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1. Mapping human tissues with highly multiplexed RNA in situ hybridization

Author

Kian Kalhor, Chien-Ju Chen, Ho Suk Lee, Matthew Cai, Mahsa Nafisi, Richard Que, Carter R. Palmer, Yixu Yuan, Yida Zhang, Xuwen Li, Jinghui Song, Amanda Knoten, Blue B. Lake, Joseph P. Gaut, C. Dirk Keene, Ed Lein, Peter V. Kharchenko, Jerold Chun, Sanjay Jain, Jian-Bing Fan, and Kun Zhang

Subjects
Science
Abstract

Abstract In situ transcriptomic techniques promise a holistic view of tissue organization and cell-cell interactions. There has been a surge of multiplexed RNA in situ mapping techniques but their application to human tissues has been limited due to their large size, general lower tissue quality and high autofluorescence. Here we report DART-FISH, a padlock probe-based technology capable of profiling hundreds to thousands of genes in centimeter-sized human tissue sections. We introduce an omni-cell type cytoplasmic stain that substantially improves the segmentation of cell bodies. Our enzyme-free isothermal decoding procedure allows us to image 121 genes in large sections from the human neocortex in 20 healthy and pathological cell states, and identified diseased niches enriched in transcriptionally altered epithelial cells and myofibroblasts.

Published
2024
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2. The chromatin landscape of healthy and injured cell types in the human kidney

Author

Debora L. Gisch, Michelle Brennan, Blue B. Lake, Jeannine Basta, Mark S. Keller, Ricardo Melo Ferreira, Shreeram Akilesh, Reetika Ghag, Charles Lu, Ying-Hua Cheng, Kimberly S. Collins, Samir V. Parikh, Brad H. Rovin, Lynn Robbins, Lisa Stout, Kimberly Y. Conklin, Dinh Diep, Bo Zhang, Amanda Knoten, Daria Barwinska, Mahla Asghari, Angela R. Sabo, Michael J. Ferkowicz, Timothy A. Sutton, Katherine J. Kelly, Ian H. De Boer, Sylvia E. Rosas, Krzysztof Kiryluk, Jeffrey B. Hodgin, Fadhl Alakwaa, Seth Winfree, Nichole Jefferson, Aydın Türkmen, Joseph P. Gaut, Nils Gehlenborg, Carrie L. Phillips, Tarek M. El-Achkar, Pierre C. Dagher, Takashi Hato, Kun Zhang, Jonathan Himmelfarb, Matthias Kretzler, Shamim Mollah, the Kidney Precision Medicine Project (KPMP), Sanjay Jain, Michael Rauchman, and Michael T. Eadon

Subjects
Science
Abstract

Abstract There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidney’s active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we note distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3, KLF6, and KLF10 regulates the transition between health and injury, while in thick ascending limb cells this transition is regulated by NR2F1. Further, combined perturbation of ELF3, KLF6, and KLF10 distinguishes two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks.

Published
2024
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3. A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease

Author

Victor Hugo Canela, William S. Bowen, Ricardo Melo Ferreira, Farooq Syed, James E. Lingeman, Angela R. Sabo, Daria Barwinska, Seth Winfree, Blue B. Lake, Ying-Hua Cheng, Joseph P. Gaut, Michael Ferkowicz, Kaice A. LaFavers, Kun Zhang, Fredric L. Coe, Elaine Worcester, the Kidney Precision Medicine Project, Sanjay Jain, Michael T. Eadon, James C. Williams, and Tarek M. El-Achkar

Subjects
Science
Abstract

Abstract Kidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers.

Published
2023
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4. Cellular Recruitment by Podocyte-Derived Pro-migratory Factors in Assembly of the Human Renal Filter

Author

Albert D. Kim, Blue B. Lake, Song Chen, Yan Wu, Jinjin Guo, Riana K. Parvez, Tracy Tran, Matthew E. Thornton, Brendan Grubbs, Jill A. McMahon, Kun Zhang, and Andrew P. McMahon

Subjects
Science
Abstract

Summary: Analysis of kidney disease-causing genes and pathology resulting from systemic diseases highlight the importance of the kidney's filtering system, the renal corpuscles. To elucidate the developmental processes that establish the renal corpuscle, we performed single-nucleus droplet-based sequencing of the human fetal kidney. This enabled the identification of nephron, interstitial, and vascular cell types that together generate the renal corpuscles. Trajectory analysis identified transient developmental gene expression, predicting precursors or mature podocytes express FBLN2, BMP4, or NTN4, in conjunction with recruitment, differentiation, and modeling of vascular and mesangial cell types into a functional filter. In vitro studies provide evidence that these factors exhibit angiogenic or mesangial recruiting and inductive properties consistent with a key organizing role for podocyte precursors in kidney development. Together these studies define a spatiotemporal developmental program for the primary filtration unit of the human kidney and provide novel insights into cell interactions regulating co-assembly of constituent cell types. : Biological Sciences; Cell Biology; Developmental Biology; Omics Subject Areas: Biological Sciences, Cell Biology, Developmental Biology, Omics

Published
2019
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5. A single-nucleus RNA-sequencing pipeline to decipher the molecular anatomy and pathophysiology of human kidneys

Author

Blue B. Lake, Song Chen, Masato Hoshi, Nongluk Plongthongkum, Diane Salamon, Amanda Knoten, Anitha Vijayan, Ramakrishna Venkatesh, Eric H. Kim, Derek Gao, Joseph Gaut, Kun Zhang, and Sanjay Jain

Subjects
Science
Abstract

Single-cell studies in solid tissues remain challenging and have benefited from the development of single-nuclei RNA sequencing strategies. Here Lake et al. apply single-nucleus RNA sequencing to human kidney tissues to provide a comprehensive molecular and cellular atlas of the human kidney, with potential implications for the understanding of kidney physiology and disease.

Published
2019
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6. The role of the NMD factor UPF3B in olfactory sensory neurons

Author

Kun Tan, Samantha H Jones, Blue B Lake, Jennifer N Chousal, Eleen Y Shum, Lingjuan Zhang, Song Chen, Abhishek Sohni, Shivam Pandya, Richard L Gallo, Kun Zhang, Heidi Cook-Andersen, and Miles F Wilkinson

Subjects
NMD, Upf3b, olfactory sensory neuron, scRNA-seq, olfactory receptor, anti-microbial genes, Medicine, Science, Biology (General), QH301-705.5
Abstract

The UPF3B-dependent branch of the nonsense-mediated RNA decay (NMD) pathway is critical for human cognition. Here, we examined the role of UPF3B in the olfactory system. Single-cell RNA-sequencing (scRNA-seq) analysis demonstrated considerable heterogeneity of olfactory sensory neuron (OSN) cell populations in wild-type (WT) mice, and revealed that UPF3B loss influences specific subsets of these cell populations. UPF3B also regulates the expression of a large cadre of antimicrobial genes in OSNs, and promotes the selection of specific olfactory receptor (Olfr) genes for expression in mature OSNs (mOSNs). RNA-seq and Ribotag analyses identified classes of mRNAs expressed and translated at different levels in WT and Upf3b-null mOSNs. Integrating multiple computational approaches, UPF3B-dependent NMD target transcripts that are candidates to mediate the functions of NMD in mOSNs were identified in vivo. Together, our data provides a valuable resource for the olfactory field and insights into the roles of NMD in vivo.

Published
2020
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7. A comparative strategy for single-nucleus and single-cell transcriptomes confirms accuracy in predicted cell-type expression from nuclear RNA

Author

Blue B. Lake, Simone Codeluppi, Yun C. Yung, Derek Gao, Jerold Chun, Peter V. Kharchenko, Sten Linnarsson, and Kun Zhang

Subjects
Medicine, Science
Abstract

Abstract Significant heterogeneities in gene expression among individual cells are typically interrogated using single whole cell approaches. However, tissues that have highly interconnected processes, such as in the brain, present unique challenges. Single-nucleus RNA sequencing (SNS) has emerged as an alternative method of assessing a cell’s transcriptome through the use of isolated nuclei. However, studies directly comparing expression data between nuclei and whole cells are lacking. Here, we have characterized nuclear and whole cell transcriptomes in mouse single neurons and provided a normalization strategy to reduce method-specific differences related to the length of genic regions. We confirmed a high concordance between nuclear and whole cell transcriptomes in the expression of cell type and metabolic modeling markers, but less so for a subset of genes associated with mitochondrial respiration. Therefore, our results indicate that single-nucleus transcriptome sequencing provides an effective means to profile cell type expression dynamics in previously inaccessible tissues.

Published
2017
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8. The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment

Author

Hye-Won Song, Anilkumar Bettegowda, Blue B. Lake, Adrienne H. Zhao, David Skarbrevik, Eric Babajanian, Meena Sukhwani, Eleen Y. Shum, Mimi H. Phan, Terra-Dawn M. Plank, Marcy E. Richardson, Madhuvanthi Ramaiah, Vaishnavi Sridhar, Dirk G. de Rooij, Kyle E. Orwig, Kun Zhang, and Miles F. Wilkinson

Subjects
spermatogonial stem cells, spermatogonia, spermatogenesis, germ cell, germ line stem cell, homeobox, Rhox, transcription factor, gonocytes, prospermatogonia, Biology (General), QH301-705.5
Abstract

The developmental origins of most adult stem cells are poorly understood. Here, we report the identification of a transcription factor—RHOX10—critical for the initial establishment of spermatogonial stem cells (SSCs). Conditional loss of the entire 33-gene X-linked homeobox gene cluster that includes Rhox10 causes progressive spermatogenic decline, a phenotype indistinguishable from that caused by loss of only Rhox10. We demonstrate that this phenotype results from dramatically reduced SSC generation. By using a battery of approaches, including single-cell-RNA sequencing (scRNA-seq) analysis, we show that Rhox10 drives SSC generation by promoting pro-spermatogonia differentiation. Rhox10 also regulates batteries of migration genes and promotes the migration of pro-spermatogonia into the SSC niche. The identification of an X-linked homeobox gene that drives the initial generation of SSCs has implications for the evolution of X-linked gene clusters and sheds light on regulatory mechanisms influencing adult stem cell generation in general.

Published
2016
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9. Observation of Wigner cusps in a metallic carbon nanotube

Author

Blue, B. T., Tsuchikawa, R., Ahmadi, A., Zhang, Z., Heligman, D., Lough, S. D., Hone, J., Mucciolo, E. R., and Ishigami, M.

Subjects
Condensed Matter - Mesoscale and Nanoscale Physics, Quantum Physics
Abstract

Previous gate-dependent conductance measurements of metallic carbon nanotubes have revealed unexplainable conductance suppressions, occurring at two different gate voltages. These were previously attributed to the gate-dependency of contact resistance. Our gate-dependent conductivity measurements on a metallic nanotube with known chirality show that these bimodal conductance suppressions are the manifestations of Wigner cusps, often seen in atomic and nuclear physics experiments., Comment: 6 pages, 3 figures

Published
2023
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10. Early Head Specification in Xenopus laevis

Author

Blue B. Lake and Kenneth R. Kao

Subjects
Technology, Medicine, Science
Abstract

The head represents the most dorsal and anterior extent of the body axis. In Xenopus, the progressive determination of the head is an extremely complex process involving the activation and localized antagonism of a number of interdependent intracellular signaling pathways including the Wingless/Int-1 (Wnt), bone morphogenetic protein (BMP), and nodal-related pathways. The sequence of events that specify the head are: dorsal-ventral polarization and head organizer specification in the blastula; gastrulation; neural induction; and patterning of the anterior-posterior and dorsal-ventral neuraxes. Wnt signaling is required for the specification of the dorsal side initially but is then inhibited within the organizer once it has formed. Similarly, Wnt signaling is required along the length of the neural tube, but must be suppressed at its rostral end for normal brain development. Nodal signaling is also necessary for induction of the mesendoderm, but is subsequently suppressed in its dorsal-anterior extreme to specify head organizer. BMP signaling is required for ventral mesoderm and non-neural ectoderm, and must also be suppressed in the head organizer region and for the differentiation of the ventral midline of the neural tube. Thus, development of the head, and indeed the body plan in general, requires precisely timed and spatially restricted activation and repression of these signaling pathways.

Published
2003
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11. A reference tissue atlas for the human kidney

Author

Hansen, Jens, Sealfon, Rachel, Menon, Rajasree, Eadon, Michael T, Lake, Blue B, Steck, Becky, Anjani, Kavya, Parikh, Samir, Sigdel, Tara K, Zhang, Guanshi, Velickovic, Dusan, Barwinska, Daria, Alexandrov, Theodore, Dobi, Dejan, Rashmi, Priyanka, Otto, Edgar A, Rivera, Miguel, Rose, Michael P, Anderton, Christopher R, Shapiro, John P, Pamreddy, Annapurna, Winfree, Seth, Xiong, Yuguang, He, Yongqun, de Boer, Ian H, Hodgin, Jeffrey B, Barisoni, Laura, Naik, Abhijit S, Sharma, Kumar, Sarwal, Minnie M, Zhang, Kun, Himmelfarb, Jonathan, Rovin, Brad, El-Achkar, Tarek M, Laszik, Zoltan, He, John Cijiang, Dagher, Pierre C, Valerius, M Todd, Jain, Sanjay, Satlin, Lisa M, Troyanskaya, Olga G, Kretzler, Matthias, Iyengar, Ravi, Azeloglu, Evren U, and Project, Kidney Precision Medicine

Subjects
Biotechnology, Genetics, Kidney Disease, Aetiology, 2.1 Biological and endogenous factors, Underpinning research, 1.1 Normal biological development and functioning, Generic health relevance, Renal and urogenital, Good Health and Well Being, Humans, Kidney, Kidney Diseases, Metabolomics, Proteomics, Transcriptome, Kidney Precision Medicine Project
Abstract

Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map of cells, pathways, and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics and proteomics, near-single-cell proteomics, 3D and CODEX imaging, and spatial metabolomics to hierarchically identify genes, pathways, and cells. Integrated data from these different technologies coherently identify cell types/subtypes within different nephron segments and the interstitium. These profiles describe cell-level functional organization of the kidney following its physiological functions and link cell subtypes to genes, proteins, metabolites, and pathways. They further show that messenger RNA levels along the nephron are congruent with the subsegmental physiological activity. This reference atlas provides a framework for the classification of kidney disease when multiple molecular mechanisms underlie convergent clinical phenotypes.

Published
2022

12. An atlas of healthy and injured cell states and niches in the human kidney

Author

Lake, Blue B., Menon, Rajasree, Winfree, Seth, Hu, Qiwen, Melo Ferreira, Ricardo, Kalhor, Kian, Barwinska, Daria, Otto, Edgar A., Ferkowicz, Michael, Diep, Dinh, Plongthongkum, Nongluk, Knoten, Amanda, Urata, Sarah, Mariani, Laura H., Naik, Abhijit S., Eddy, Sean, Zhang, Bo, Wu, Yan, Salamon, Diane, Williams, James C., Wang, Xin, Balderrama, Karol S., Hoover, Paul J., Murray, Evan, Marshall, Jamie L., Noel, Teia, Vijayan, Anitha, Hartman, Austin, Chen, Fei, Waikar, Sushrut S., Rosas, Sylvia E., Wilson, Francis P., Palevsky, Paul M., Kiryluk, Krzysztof, Sedor, John R., Toto, Robert D., Parikh, Chirag R., Kim, Eric H., Satija, Rahul, Greka, Anna, Macosko, Evan Z., Kharchenko, Peter V., Gaut, Joseph P., Hodgin, Jeffrey B., Eadon, Michael T., Dagher, Pierre C., El-Achkar, Tarek M., Zhang, Kun, Kretzler, Matthias, and Jain, Sanjay

Published
2023
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13. A genetic algorithm approach to reconstructing spectral content from filtered x-ray diode array spectrometers

Author

Kemp, G. E., Rubery, M. S., Harris, C. D., May, M. J., Widmann, K., Heeter, R. F., Libby, S. B., Schneider, M. B., and Blue, B. E.

Subjects
Physics - Computational Physics, Physics - Atomic Physics, Physics - Data Analysis, Statistics and Probability, Physics - Instrumentation and Detectors
Abstract

Filtered diode array spectrometers are routinely employed to infer the temporal evolution of spectral power from x-ray sources, but uniquely extracting spectral content from a finite set of broad, spectrally overlapping channel spectral sensitivities is decidedly nontrivial in these underdetermined systems. We present the use of genetic algorithms to reconstruct a probabilistic spectral intensity distribution and compare to the traditional approach most commonly found in literature. Unlike many of the previously published models, spectral reconstructions from this approach are neither limited by basis functional forms, nor do they require a priori spectral knowledge. While the original intent of such measurements was to diagnose the temporal evolution of spectral power from quasi-blackbody radiation sources, where the exact details of spectral content was not thought to be crucial, we demonstrate that this new technique can greatly enhance the utility of the diagnostic by providing more physical spectra and improved robustness to hardware configuration for even strongly non-Planckian distributions.

Published
2020

14. Comparative cellular analysis of motor cortex in human, marmoset and mouse

Author

Bakken, Trygve E, Jorstad, Nikolas L, Hu, Qiwen, Lake, Blue B, Tian, Wei, Kalmbach, Brian E, Crow, Megan, Hodge, Rebecca D, Krienen, Fenna M, Sorensen, Staci A, Eggermont, Jeroen, Yao, Zizhen, Aevermann, Brian D, Aldridge, Andrew I, Bartlett, Anna, Bertagnolli, Darren, Casper, Tamara, Castanon, Rosa G, Crichton, Kirsten, Daigle, Tanya L, Dalley, Rachel, Dee, Nick, Dembrow, Nikolai, Diep, Dinh, Ding, Song-Lin, Dong, Weixiu, Fang, Rongxin, Fischer, Stephan, Goldman, Melissa, Goldy, Jeff, Graybuck, Lucas T, Herb, Brian R, Hou, Xiaomeng, Kancherla, Jayaram, Kroll, Matthew, Lathia, Kanan, van Lew, Baldur, Li, Yang Eric, Liu, Christine S, Liu, Hanqing, Lucero, Jacinta D, Mahurkar, Anup, McMillen, Delissa, Miller, Jeremy A, Moussa, Marmar, Nery, Joseph R, Nicovich, Philip R, Niu, Sheng-Yong, Orvis, Joshua, Osteen, Julia K, Owen, Scott, Palmer, Carter R, Pham, Thanh, Plongthongkum, Nongluk, Poirion, Olivier, Reed, Nora M, Rimorin, Christine, Rivkin, Angeline, Romanow, William J, Sedeño-Cortés, Adriana E, Siletti, Kimberly, Somasundaram, Saroja, Sulc, Josef, Tieu, Michael, Torkelson, Amy, Tung, Herman, Wang, Xinxin, Xie, Fangming, Yanny, Anna Marie, Zhang, Renee, Ament, Seth A, Behrens, M Margarita, Bravo, Hector Corrada, Chun, Jerold, Dobin, Alexander, Gillis, Jesse, Hertzano, Ronna, Hof, Patrick R, Höllt, Thomas, Horwitz, Gregory D, Keene, C Dirk, Kharchenko, Peter V, Ko, Andrew L, Lelieveldt, Boudewijn P, Luo, Chongyuan, Mukamel, Eran A, Pinto-Duarte, António, Preissl, Sebastian, Regev, Aviv, Ren, Bing, Scheuermann, Richard H, Smith, Kimberly, Spain, William J, White, Owen R, Koch, Christof, Hawrylycz, Michael, Tasic, Bosiljka, Macosko, Evan Z, McCarroll, Steven A, and Ting, Jonathan T

Subjects
Human Genome, Neurosciences, Genetics, Biotechnology, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Animals, Atlases as Topic, Callithrix, Epigenesis, Genetic, Epigenomics, Female, GABAergic Neurons, Gene Expression Profiling, Glutamates, Humans, In Situ Hybridization, Fluorescence, Male, Mice, Middle Aged, Motor Cortex, Neurons, Organ Specificity, Phylogeny, Single-Cell Analysis, Species Specificity, Transcriptome, General Science & Technology
Abstract

The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch-seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.

Published
2021

15. A multimodal cell census and atlas of the mammalian primary motor cortex

Author

Callaway, Edward M, Dong, Hong-Wei, Ecker, Joseph R, Hawrylycz, Michael J, Huang, Z Josh, Lein, Ed S, Ngai, John, Osten, Pavel, Ren, Bing, Tolias, Andreas Savas, White, Owen, Zeng, Hongkui, Zhuang, Xiaowei, Ascoli, Giorgio A, Behrens, M Margarita, Chun, Jerold, Feng, Guoping, Gee, James C, Ghosh, Satrajit S, Halchenko, Yaroslav O, Hertzano, Ronna, Lim, Byung Kook, Martone, Maryann E, Ng, Lydia, Pachter, Lior, Ropelewski, Alexander J, Tickle, Timothy L, Yang, X William, Zhang, Kun, Bakken, Trygve E, Berens, Philipp, Daigle, Tanya L, Harris, Julie A, Jorstad, Nikolas L, Kalmbach, Brian E, Kobak, Dmitry, Li, Yang Eric, Liu, Hanqing, Matho, Katherine S, Mukamel, Eran A, Naeemi, Maitham, Scala, Federico, Tan, Pengcheng, Ting, Jonathan T, Xie, Fangming, Zhang, Meng, Zhang, Zhuzhu, Zhou, Jingtian, Zingg, Brian, Armand, Ethan, Yao, Zizhen, Bertagnolli, Darren, Casper, Tamara, Crichton, Kirsten, Dee, Nick, Diep, Dinh, Ding, Song-Lin, Dong, Weixiu, Dougherty, Elizabeth L, Fong, Olivia, Goldman, Melissa, Goldy, Jeff, Hodge, Rebecca D, Hu, Lijuan, Keene, C Dirk, Krienen, Fenna M, Kroll, Matthew, Lake, Blue B, Lathia, Kanan, Linnarsson, Sten, Liu, Christine S, Macosko, Evan Z, McCarroll, Steven A, McMillen, Delissa, Nadaf, Naeem M, Nguyen, Thuc Nghi, Palmer, Carter R, Pham, Thanh, Plongthongkum, Nongluk, Reed, Nora M, Regev, Aviv, Rimorin, Christine, Romanow, William J, Savoia, Steven, Siletti, Kimberly, Smith, Kimberly, Sulc, Josef, Tasic, Bosiljka, Tieu, Michael, Torkelson, Amy, Tung, Herman, van Velthoven, Cindy TJ, Vanderburg, Charles R, Yanny, Anna Marie, Fang, Rongxin, Hou, Xiaomeng, Lucero, Jacinta D, Osteen, Julia K, Pinto-Duarte, Antonio, and Poirion, Olivier

Subjects
Genetics, Neurosciences, Human Genome, Biotechnology, Underpinning research, 1.1 Normal biological development and functioning, Neurological, Animals, Atlases as Topic, Callithrix, Epigenomics, Female, Gene Expression Profiling, Glutamates, Humans, In Situ Hybridization, Fluorescence, Male, Mice, Motor Cortex, Neurons, Organ Specificity, Phylogeny, Single-Cell Analysis, Species Specificity, Transcriptome, BRAIN Initiative Cell Census Network, General Science & Technology
Abstract

Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1-5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.

Published
2021

16. The role of the NMD factor UPF3B in olfactory sensory neurons.

Author

Tan, Kun, Jones, Samantha H, Lake, Blue B, Dumdie, Jennifer N, Shum, Eleen Y, Zhang, Lingjuan, Chen, Song, Sohni, Abhishek, Pandya, Shivam, Gallo, Richard L, Zhang, Kun, Cook-Andersen, Heidi, and Wilkinson, Miles F

Subjects
NMD, Upf3b, anti-microbial genes, developmental biology, mouse, neuroscience, olfactory receptor, olfactory sensory neuron, scRNA-seq, Biochemistry and Cell Biology
Abstract

The UPF3B-dependent branch of the nonsense-mediated RNA decay (NMD) pathway is critical for human cognition. Here, we examined the role of UPF3B in the olfactory system. Single-cell RNA-sequencing (scRNA-seq) analysis demonstrated considerable heterogeneity of olfactory sensory neuron (OSN) cell populations in wild-type (WT) mice, and revealed that UPF3B loss influences specific subsets of these cell populations. UPF3B also regulates the expression of a large cadre of antimicrobial genes in OSNs, and promotes the selection of specific olfactory receptor (Olfr) genes for expression in mature OSNs (mOSNs). RNA-seq and Ribotag analyses identified classes of mRNAs expressed and translated at different levels in WT and Upf3b-null mOSNs. Integrating multiple computational approaches, UPF3B-dependent NMD target transcripts that are candidates to mediate the functions of NMD in mOSNs were identified in vivo. Together, our data provides a valuable resource for the olfactory field and insights into the roles of NMD in vivo.

Published
2020

17. Participant Experience with Protocol Research Kidney Biopsies in the Kidney Precision Medicine Project

Author

Victoria-Castro, Angela M., Corona-Villalobos, Celia P., Xu, Alan Y., Onul, Ingrid, Huynh, Courtney, Chen, Sarah W., Ugwuowo, Ugochukwu, Sarkisova, Natalya, Dighe, Ashveena L., Blank, Kristina N., Blanc, Victoria M., Rose, Michael P., Himmelfarb, Jonathan, de Boer, Ian H., Tuttle, Katherine R., Roberts, Glenda V., Alexandrov, Theodore, Alloway, Rita R., Alpers, Charles E., Amodu, Afolarin A., Anderton, Christopher R., Anjani, Kavya, Appelbaum, Paul, Ardayfio, Joseph, Arora, Tanima, Ascani, Heather, El-Achkar, Tarek M., Aulisio, Mark, Azeloglu, Evren U., Balderes, Olivia, Balis, Ulysses G.J., Bansal, Shweta, Barasch, Jonathan M., Bansal, Shweta, Barkell, Alex, Barwinska, Daria, Basit, Mujeeb, Basta, Jeanine, Bebiak, Jack, Beck, Laurence H., Bender, Filitsa, Berglund, Ashley, Bernard, Lauren, Berrouet, Cecilia, Berry, Brooke, Bjornstad, Petter M., Blanc, Victoria M., Blank, Kristina N., Bledsoe, Sharon, Boada, Patrick, Bogen, Steve, Bomback, Andrew S., Bonevich, Nikole, Borner, Katy, Brown, Keith, Bueckle, Andreas, Burg, Ashley R., Burgess, Adam, Bush, Lakeshia, Bush, William S., Campbell, Catherine E., Campbell, Taneisha, Canetta, Pietro A., Cantley, Lloyd G., Caprioli, Richard M., Carson, Jonas, Chen, Sarah, Chen, Yijiang M., Cheng, Yinghua, Cimino, Jim, Colona, Mia R., Conser, Ninive C., Cooperman, Leslie, Crawford, Dana C., DʼAgati, Vivette D., Dagher, Pierre C., Daniel, Stephen, Daratha, Kenn, de Boer, Ian H., Diettman, Sabine M., Dighe, Ashveena L., Donohoe, Isabel, Dowd, Frederick, Dunn, Kenneth W., Eadon, Michael T., Eddy, Sean, Elder, Michele M., Ferkowicz, Michael J., Frey, Renee, Gadegbeku, Crystal A., Gaut, Joseph P., Gilliam, Matthew, Ginley, Brandon, Gisch, Debora, Goltsev, Yury, Gonzalez-Vicente, Agustin, Greka, Anna, Grewenow, Stephanie M., Hacohen, Nir, Hall, Daniel E., Hansen, Jens, Hayashi, Lynda, He, Cijang, He, Yougqun, Hedayati, S. Susan, Henderson, Joel M., Hendricks, Allen H., Herlitz, Leal, Herr, Bruce W., Himmelfarb, Jonathan, Hodgin, Jeffrey B., Hoofnagle, Andrew N., Hoover, Paul J., Ilori, Titlayo, Iyengar, Ravi, Jain, Sanjay, Jain, Yashvardhan, Janowczyk, Andrew, Jefferson, Nichole, Johansen, Camille, Jolly, Stacey, Kakade, Vijaykumar R., Kellum, John A., Kelly, Katherine J., Kermani, Asra, Kiryluk, Krzysztof, Knight, Richard, Koewler, Robert, Kretzler, Matthias, Kudose, Satoru, Lake, Blue B., Larson, Brandon, Laszik, Zoltan G., Lecker, Stewart H., Lee, Paul J., Lee, Simon C., Lienczewski, Chrysta, Limonte, Christine, Lu, Christopher Y., Lucarelli, Nicholas, Lukowski, Jessica, Luo, Jinghui, Lutnick, Brendon, Ma, Shihong, Madabhushi, Anant, Madhavan, Sethu M., Maikhor, Shana, Mariani, Laura H., Marshall, Jamie L., McClelland, Robyn L., McMahon, Gearoid M., Mehl, Karla, Ferreira, Ricardo Melo, Menez, Steven, Menon, Rajasree, Miller, R. Tyler, Moe, Orson W., Moledina, Dennis, Montellano, Richard, Mooney, Sean D., Morales, Martha Catalina, Mukatash, Tariq, Murugan, Raghavan, Nam, Yunbi, Nguyen, Jane, Nolan, Garry, Oʼtoole, John, Oliver, George (Holt), Onul, Ingrid, Otto, Edgar, Palevsky, Paul M., Palmer, Ellen, Pamreddy, Annapurna, Parikh, Chirag R., Parikh, Samir, Park, Christopher, Park, Harold, Pasa-Tolic, Ljiljana, Patel, Jiten, Patterson, Nathan, Phuong, Jim, Pillai, Anil, Pinkeney, Roy, Poggio, Emilio, Pollack, Ari, Prasad, Pottumarthi, Pyle, Laura, Quardokus, Ellen M., Randhawa, Parmjeet, Rauchman, Michael I., Record, Elizabeth, Rennke, Helmut, Rezaei, Kasra, Rike, Adele, Rivera, Marcelino, Roberts, Glenda V., Rosas, Sylvia E., Rosenberg, Avi, Rosengart, Matthew, Rovin, Brad, Roy, Neil, Sabatello, Maya, Sambandam, Kamalanathan, Sarder, Pinaki, Sarkisova, Natalya, Sarwal, Minnie, Saul, John, Schaub, Jennifer, Schmidt, Insa, Sealfon, Rachel, Sedor, John, Sendrey, Dianna, Shang, Ning, Shankland, Stuart, Shapiro, John P., Sharma, Kumar, Sharman, Kavya, Shaw, Melissa M., Shi, Tiffany, Shpigel, Anna, Sigdel, Tara, Slade, Austen, Snyder, Jamie, Spates-Harden, Kassandra, Spraggins, Jeffrey M., Srivastava, Anand, Steck, Becky, Stillman, Isaac, Stutzke, Christy, Su, Jing, Sun, Jennifer, Sutton, Timothy A., Taliercio, Jonathan, Tan, Roderick, Torrealba, Jose, Toto, Robert D., Troyanskaya, Olga, Tublin, Mitchell, Tuttle, Katherine R., Ugwuowo, Ugochukwu, Valerius, M. Todd, Van de Plas, Raf, Varela, German, Vazquez, Miguel, Velickovic, Dusan, Venkatachalam, Manjeri, Verma, Ashish, Victoria-Castro, Angela M., Vijayan, Anitha, Corona-Villalobos, Celia P., Vinovskis, Carissa, Viswanathan, Vidya S., Vita, Tina, Waikar, Sushrut, Wang, Ashley, Wang, Ruikang, Wang, Nancy, Weins, Astrid, Wen, Natasha, Wen, Yumeng, Wilcox, Adam, Williams, James C., Jr., Kayleen Williams, Williams, Mark, Wilson, Francis P., Winfree, Seth, Winters, James, Wofford, Stephanie, Wong, Aaron, Woodle, E. Steve, Xiong, Yuguang, Xu, Alan, Yadati, Pranav, Ye, Hongping, Yu, Guanghao, Zhang, Dianbo, Zhang, Guanshi, and Zhang, Kun

Published
2024
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18. High-throughput sequencing of the transcriptome and chromatin accessibility in the same cell

Author

Chen, Song, Lake, Blue B, and Zhang, Kun

Subjects
Biotechnology, Genetics, Human Genome, Stem Cell Research, 1.1 Normal biological development and functioning, Underpinning research, Generic health relevance, Animals, Cells, Cultured, Cerebral Cortex, Chromatin, Computational Biology, High-Throughput Nucleotide Sequencing, Mice, RNA, Messenger, Sequence Analysis, RNA, Transcriptome
Abstract

Single-cell RNA sequencing can reveal the transcriptional state of cells, yet provides little insight into the upstream regulatory landscape associated with open or accessible chromatin regions. Joint profiling of accessible chromatin and RNA within the same cells would permit direct matching of transcriptional regulation to its outputs. Here, we describe droplet-based single-nucleus chromatin accessibility and mRNA expression sequencing (SNARE-seq), a method that can link a cell's transcriptome with its accessible chromatin for sequencing at scale. Specifically, accessible sites are captured by Tn5 transposase in permeabilized nuclei to permit, within many droplets in parallel, DNA barcode tagging together with the mRNA molecules from the same cells. To demonstrate the utility of SNARE-seq, we generated joint profiles of 5,081 and 10,309 cells from neonatal and adult mouse cerebral cortices, respectively. We reconstructed the transcriptome and epigenetic landscapes of major and rare cell types, uncovered lineage-specific accessible sites, especially for low-abundance cells, and connected the dynamics of promoter accessibility with transcription level during neurogenesis.

Published
2019

19. Cellular Recruitment by Podocyte-Derived Pro-migratory Factors in Assembly of the Human Renal Filter

Author

Kim, Albert D, Lake, Blue B, Chen, Song, Wu, Yan, Guo, Jinjin, Parvez, Riana K, Tran, Tracy, Thornton, Matthew E, Grubbs, Brendan, McMahon, Jill A, Zhang, Kun, and McMahon, Andrew P

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Kidney Disease, Underpinning research, 1.1 Normal biological development and functioning, Renal and urogenital, Cell Biology, Developmental Biology, Omics
Abstract

Analysis of kidney disease-causing genes and pathology resulting from systemic diseases highlight the importance of the kidney's filtering system, the renal corpuscles. To elucidate the developmental processes that establish the renal corpuscle, we performed single-nucleus droplet-based sequencing of the human fetal kidney. This enabled the identification of nephron, interstitial, and vascular cell types that together generate the renal corpuscles. Trajectory analysis identified transient developmental gene expression, predicting precursors or mature podocytes express FBLN2, BMP4, or NTN4, in conjunction with recruitment, differentiation, and modeling of vascular and mesangial cell types into a functional filter. In vitro studies provide evidence that these factors exhibit angiogenic or mesangial recruiting and inductive properties consistent with a key organizing role for podocyte precursors in kidney development. Together these studies define a spatiotemporal developmental program for the primary filtration unit of the human kidney and provide novel insights into cell interactions regulating co-assembly of constituent cell types.

Published
2019

20. A single-nucleus RNA-sequencing pipeline to decipher the molecular anatomy and pathophysiology of human kidneys.

Author

Lake, Blue B, Chen, Song, Hoshi, Masato, Plongthongkum, Nongluk, Salamon, Diane, Knoten, Amanda, Vijayan, Anitha, Venkatesh, Ramakrishna, Kim, Eric H, Gao, Derek, Gaut, Joseph, Zhang, Kun, and Jain, Sanjay

Subjects
Kidney, Cell Nucleus, Humans, Kidney Diseases, Gene Expression Profiling, Sequence Analysis, RNA, Aged, Middle Aged, Female, Male, Mesangial Cells, Single-Cell Analysis, Sequence Analysis, RNA
Abstract

Defining cellular and molecular identities within the kidney is necessary to understand its organization and function in health and disease. Here we demonstrate a reproducible method with minimal artifacts for single-nucleus Droplet-based RNA sequencing (snDrop-Seq) that we use to resolve thirty distinct cell populations in human adult kidney. We define molecular transition states along more than ten nephron segments spanning two major kidney regions. We further delineate cell type-specific expression of genes associated with chronic kidney disease, diabetes and hypertension, providing insight into possible targeted therapies. This includes expression of a hypertension-associated mechano-sensory ion channel in mesangial cells, and identification of proximal tubule cell populations defined by pathogenic expression signatures. Our fully optimized, quality-controlled transcriptomic profiling pipeline constitutes a tool for the generation of healthy and diseased molecular atlases applicable to clinical samples.

Published
2019

21. A Participant-Centered Approach to Understanding Risks and Benefits of Participation in Research Informed by the Kidney Precision Medicine Project

Author

Alexandrov, Theodore, Alpers, Charles E., Anderton, Christopher R., Ardayfio, Joseph, Arora, Tanima, El-Achkar, Tarek M., Azeloglu, Evren U., Balderes, Olivia, Balis, Ulysses G.J., Bansal, Shweta, Barasch, Jonathan M., Barwinska, Daria, Bebiak, Jack, Blanc, Victoria M., Blank, Kristina N., Bomback, Andrew S., Brown, Keith D., Bush, William S., Campbell, Taneisha, Canetta, Pietro A., Carson, Jonas, Cooperman, Leslie, Crawford, Dana C., D’Agati, Vivette D., Dagher, Pierre C., Daniel, Stephen, Dowd, Frederick, Dunn, Kenneth W., Eadon, Michael T., Eddy, Sean, Elder, Michele M., Ferkowicz, Michael J., Gaut, Joe P., Goltsev, Yury, Gonzalez-Vicente, Agustin, Hacohen, Nir, Hansen, Jens, Hayashi, Lynda, He, Oliver, He, Cijang, Hedayati, S. Susan, Herlitz, Leal, Hodgin, Jeffrey B., Hoofnagle, Andrew N., Hoover, Paul J., Iyengar, Ravi, Jain, Sanjay, Jefferson, Nichole, Jolly, Stacey, Kellum, John A., Kelly, Katherine J., Kermani, Asra, Kiryluk, Krzysztof, Koewler, Robert, Kretzler, Matthias, Lake, Blue B., Laszik, Zoltan G., Lecker, Stewart H., Lee, Simon C., Lienczewski, Chrysta, Lu, Christopher Y., Mariani, Laura H., McClelland, Robyn L., McMahon, Gearoid M., Menez, Steven, Menon, Rajasree, Miller, Tyler, Moe, Orson W., Moledina, Dennis, Mooney, Sean D., Nguyen, Jane, Nolan, Garry, Oliver, George, Otto, Edgar, Palevsky, Paul M., Palmer, Ellen, Pamreddy, Annapurna, Parikh, Chirag R., Parikh, Samir, Park, Christopher, Park, Harold, Pasa-Tolic, Ljiljana, Pinkeney, Roy, Poggio, Emilio, Randhawa, Parmjeet, Rennke, Helmut, Roberts, Glenda V., Rosenberg, Avi, Rosengart, Matthew, Rovin, Brad, Roy, Neil, Sambandam, Kamalanathan, Sarwal, Minnie, Saul, John, Schaub, Jennifer, Sealfon, Rachel, Shang, Ning, Shankland, Stuart, Sharma, Kumar, Shpigel, Anna, Sigdel, Tara, Steck, Becky, Stillman, Isaac, Stutzke, Edith Christine, Sutton, Timothy A., Torrealba, Jose, Toto, Robert D., Troyanskaya, Olga, Tublin, Mitchell, Ugwuowo, Ugochukwu, Vazquez, Miguel, Velickovic, Dusan, Venkatachalam, Manjeri, Vijayan, Anitha, Corona-Villalobos, Celia P., Wang, Nancy, Weins, Astrid, Wilcox, Adam, Williams, Kayleen, Williams, Mark, Wilson, Francis P., Winfree, Seth, Xiong, Yuguang, Zhang, Kun, Zhang, Guanshi, Butler, Catherine R., Appelbaum, Paul S., Ascani, Heather, Aulisio, Mark, Campbell, Catherine E., de Boer, Ian H., Dighe, Ashveena L., Hall, Daniel E., Himmelfarb, Jonathan, Knight, Richard, Mehl, Karla, Murugan, Raghavan, Rosas, Sylvia E., Sedor, John R., O’Toole, John F., Tuttle, Katherine R., Waikar, Sushrut S., and Freeman, Michael

Published
2022
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22. When Shock Waves Collide

Author

Hartigan, P., Foster, J., Frank, A., Hansen, E., Yirak, K., Liao, A. S., Graham, P., Wilde, B., Blue, B., Martinez, D., Rosen, P., Farley, D., and Paguio, R.

Subjects
Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

Supersonic outflows from objects as varied as stellar jets, massive stars and novae often exhibit multiple shock waves that overlap one another. When the intersection angle between two shock waves exceeds a critical value, the system reconfigures its geometry to create a normal shock known as a Mach stem where the shocks meet. Mach stems are important for interpreting emission-line images of shocked gas because a normal shock produces higher postshock temperatures and therefore a higher-excitation spectrum than an oblique one does. In this paper we summarize the results of a series of numerical simulations and laboratory experiments designed to quantify how Mach stems behave in supersonic plasmas that are the norm in astrophysical flows. The experiments test analytical predictions for critical angles where Mach stems should form, and quantify how Mach stems grow and decay as intersection angles between the incident shock and a surface change. While small Mach stems are destroyed by surface irregularities and subcritical angles, larger ones persist in these situations, and can regrow if the intersection angle changes to become more favorable. The experimental and numerical results show that although Mach stems occur only over a limited range of intersection angles and size scales, within these ranges they are relatively robust, and hence are a viable explanation for variable bright knots observed in HST images at the intersections of some bow shocks in stellar jets., Comment: 2016, accepted by the Astrophysical Journal

Published
2016
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23. Cadherin-11, Sparc-related modular calcium binding protein-2, and Pigment epithelium-derived factor are promising non-invasive biomarkers of kidney fibrosis

Author

Knight, Richard, Lecker, Stewart H., Stillman, Isaac, Bogen, Steve, Amodu, Afolarin A., Ilori, Titlayo, Maikhor, Shana, Schmidt, Insa M., Beck, Laurence H., Henderson, Joel M., Onul, Ingrid, Verma, Ashish, McMahon, Gearoid M., Valerius, M. Todd, Waikar, Sushrut, Weins, Astrid, Colona, Mia R., Greka, Anna, Hacohen, Nir, Hoover, Paul J., Marshall, Jamie L., Aulisio, Mark, Chen, Yijiang M., Janowczyk, Andrew, Jayapandian, Catherine, Viswanathan, Vidya S., Bush, William S., Crawford, Dana C., Madabhushi, Anant, Bush, Lakeshia, Cooperman, Leslie, Gonzalez-Vicente, Agustin, Herlitz, Leal, Jolly, Stacey, Nguyen, Jane, O’toole, John, Palmer, Ellen, Poggio, Emilio, Sedor, John, Sendrey, Dianna, Spates-Harden, Kassandra, Taliercio, Jonathan, Bjornstad, Petter M., Pyle, Laura, Vinovskis, Carissa, Appelbaum, Paul, Balderes, Olivia, Barasch, Jonathan M., Bomback, Andrew S., Canetta, Pietro A., D’Agati, Vivette D., Kiryluk, Krzysztof, Kudose, Satoru, Mehl, Karla, Shang, Ning, Bansal, Shweta, Alexandrov, Theodore, Rennke, Helmut, El-Achkar, Tarek M., Barwinska, Daria, Bledso, Sharon, Borner, Katy, Bueckle, Andreas, Cheng, Yinghua, Dagher, Pierre C., Dunn, Kenneth W., Eadon, Michael T., Ferkowicz, Michael J., Herr, Bruce W., Kelly, Katherine J., Ferreira, Ricardo Melo, Quardokus, Ellen M., Record, Elizabeth, Rivera, Marcelino, Su, Jing, Sutton, Timothy A., Williams, James C., Jr., Winfree, Seth, Jain, Yashvardhan, Menez, Steven, Parikh, Chirag R., Rosenberg, Avi, Corona-Villalobos, Celia P., Wen, Yumeng, Johansen, Camille, Rosas, Sylvia E., Roy, Neil, Sun, Jennifer, Williams, Mark, Azeloglu, Evren U., Hansen, Jens, He, Cijang, Iyengar, Ravi, Xiong, Yuguang, Prasad, Pottumarthi, Srivastava, Anand, Madhavan, Sethu M., Parikh, Samir, Rovin, Brad, Shapiro, John P., Anderton, Christopher R., Lukowski, Jessica, Pasa-Tolic, Ljiljana, Velickovic, Dusan, Oliver, George (Holt), Ardayfio, Joseph, Bebiak, Jack, Brown, Keith, Campbell, Taneisha, Campbell, Catherine E., Hayashi, Lynda, Jefferson, Nichole, Roberts, Glenda V., Saul, John, Shpigel, Anna, Stutzke, Christy, Koewler, Robert, Pinkeney, Roy, Sealfon, Rachel, Troyanskaya, Olga, Wong, Aaron, Tuttle, Katherine R., Pollack, Ari, Goltsev, Yury, Ginley, Brandon, Lucarelli, Nicholas, Lutnick, Brendon, Sarder, Pinaki, Lake, Blue B., Zhang, Kun, Boada, Patrick, Laszik, Zoltan G., Nolan, Garry, Anjani, Kavya, Sarwal, Minnie, Mukatash, Tariq, Sigdel, Tara, Alloway, Rita R., Burg, Ashley R., Lee, Paul J., Rike, Adele, Shi, Tiffany, Woodle, E. Steve, Ascani, Heather, Balis, Ulysses G.J., Blanc, Victoria M., Conser, Ninive C., Eddy, Sean, Frey, Renee, He, Yougqun, Hodgin, Jeffrey B., Kretzler, Matthias, Lienczewski, Chrysta, Luo, Jinghui, Mariani, Laura H., Menon, Rajasree, Otto, Edgar, Schaub, Jennifer, Steck, Becky, Elder, Michele M., Gilliam, Matthew, Hall, Daniel E., Murugan, Raghavan, Palevsky, Paul M., Randhawa, Parmjeet, Rosengart, Matthew, Tublin, Mitchell, Vita, Tina, Winters, James, Kellum, John A., Alpers, Charles E., Berglund, Ashley, Berry, Brooke, Blank, Kristina N., Carson, Jonas, Daniel, Stephen, De Boer, Ian H., Dighe, Ashveena L., Dowd, Frederick, Grewenow, Stephanie M., Himmelfarb, Jonathan, Hoofnagle, Andrew N., Limonte, Christine, McClelland, Robyn L., Mooney, Sean D., Rezaei, Kasra, Shankland, Stuart, Snyder, Jamie, Wang, Ruikang, Wilcox, Adam, Williams, Kayleen, Park, Christopher, Montellano, Richard, Pamreddy, Annapurna, Sharma, Kumar, Venkatachalam, Manjeri, Ye, Hongping, Zhang, Guanshi, Basit, Mujeeb, Hedayati, S. Susan, Kermani, Asra, Lee, Simon C., Lu, Christopher Y., Miller, R. Tyler, Moe, Orson W., Patel, Jiten, Pillai, Anil, Sambandam, Kamalanathan, Torrealba, Jose, Toto, Robert D., Vazquez, Miguel, Wang, Nancy, Wen, Natasha, Zhang, Dianbo, Park, Harold, Caprioli, Richard M., Patterson, Nathan, Sharman, Kavya, Spraggins, Jeffrey M., Van de Plas, Raf, Basta, Jeanine, Diettman, Sabine M., Gaut, Joseph P., Jain, Sanjay, Rauchman, Michael I., Vijayan, Anitha, Cantley, Lloyd G., Kakade, Vijaykumar R., Moledina, Dennis, Shaw, Melissa M., Ugwuowo, Ugochukwu, Wilson, Francis P., Arora, Tanima, Kestenbaum, Bryan R., Alexopoulos, Leonidas G., Palsson, Ragnar, Liu, Jing, Stillman, Isaac E., Rennke, Helmut G., Vaidya, Vishal S., Wu, Haojia, Humphreys, Benjamin D., and Waikar, Sushrut S.

Published
2021
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24. Integrative single-cell analysis of transcriptional and epigenetic states in the human adult brain

Author

Lake, Blue B, Chen, Song, Sos, Brandon C, Fan, Jean, Kaeser, Gwendolyn E, Yung, Yun C, Duong, Thu E, Gao, Derek, Chun, Jerold, Kharchenko, Peter V, and Zhang, Kun

Subjects
Neurological, Generic health relevance, Adult, Brain, Cerebellum, Epigenesis, Genetic, Frontal Lobe, High-Throughput Nucleotide Sequencing, Humans, Sequence Analysis, RNA, Single-Cell Analysis, Transcriptome, Visual Cortex
Abstract

Detailed characterization of the cell types in the human brain requires scalable experimental approaches to examine multiple aspects of the molecular state of individual cells, as well as computational integration of the data to produce unified cell-state annotations. Here we report improved high-throughput methods for single-nucleus droplet-based sequencing (snDrop-seq) and single-cell transposome hypersensitive site sequencing (scTHS-seq). We used each method to acquire nuclear transcriptomic and DNA accessibility maps for >60,000 single cells from human adult visual cortex, frontal cortex, and cerebellum. Integration of these data revealed regulatory elements and transcription factors that underlie cell-type distinctions, providing a basis for the study of complex processes in the brain, such as genetic programs that coordinate adult remyelination. We also mapped disease-associated risk variants to specific cellular populations, which provided insights into normal and pathogenic cellular processes in the human brain. This integrative multi-omics approach permits more detailed single-cell interrogation of complex organs and tissues.

Published
2018

25. A comparative strategy for single-nucleus and single-cell transcriptomes confirms accuracy in predicted cell-type expression from nuclear RNA.

Author

Lake, Blue B, Codeluppi, Simone, Yung, Yun C, Gao, Derek, Chun, Jerold, Kharchenko, Peter V, Linnarsson, Sten, and Zhang, Kun

Subjects
Cerebral Cortex, Neurons, Cell Nucleus, Animals, Mice, Gene Expression Profiling, Organ Specificity, Gene Expression Regulation, Female, Male, Single-Cell Analysis, High-Throughput Nucleotide Sequencing, Transcriptome, Human Genome, Genetics, Biotechnology, 1.1 Normal biological development and functioning, Biochemistry and Cell Biology, Other Physical Sciences
Abstract

Significant heterogeneities in gene expression among individual cells are typically interrogated using single whole cell approaches. However, tissues that have highly interconnected processes, such as in the brain, present unique challenges. Single-nucleus RNA sequencing (SNS) has emerged as an alternative method of assessing a cell's transcriptome through the use of isolated nuclei. However, studies directly comparing expression data between nuclei and whole cells are lacking. Here, we have characterized nuclear and whole cell transcriptomes in mouse single neurons and provided a normalization strategy to reduce method-specific differences related to the length of genic regions. We confirmed a high concordance between nuclear and whole cell transcriptomes in the expression of cell type and metabolic modeling markers, but less so for a subset of genes associated with mitochondrial respiration. Therefore, our results indicate that single-nucleus transcriptome sequencing provides an effective means to profile cell type expression dynamics in previously inaccessible tissues.

Published
2017

27. The Human Tumor Atlas Network: Charting Tumor Transitions across Space and Time at Single-Cell Resolution

Author

Aberle, Denise, Achilefu, Samuel I., Ademuyiwa, Foluso O., Adey, Andrew C., Aft, Rebecca L., Agarwal, Rachana, Aguilar, Ruben A., Alikarami, Fatemeh, Allaj, Viola, Amos, Christopher, Anders, Robert A., Angelo, Michael R., Anton, Kristen, Ashenberg, Orr, Aster, Jon C., Babur, Ozgun, Bahmani, Amir, Balsubramani, Akshay, Barrett, David, Beane, Jennifer, Bender, Diane E., Bernt, Kathrin, Berry, Lynne, Betts, Courtney B., Bletz, Julie, Blise, Katie, Boire, Adrienne, Boland, Genevieve, Borowsky, Alexander, Bosse, Kristopher, Bott, Matthew, Boyden, Ed, Brooks, James, Bueno, Raphael, Burlingame, Erik A., Cai, Qiuyin, Campbell, Joshua, Caravan, Wagma, Cerami, Ethan, Chaib, Hassan, Chan, Joseph M., Chang, Young Hwan, Chatterjee, Deyali, Chaudhary, Ojasvi, Chen, Alyce A., Chen, Bob, Chen, Changya, Chen, Chia-hui, Chen, Feng, Chen, Yu-An, Chheda, Milan G., Chin, Koei, Chiu, Roxanne, Chu, Shih-Kai, Chuaqui, Rodrigo, Chun, Jaeyoung, Cisneros, Luis, Coffey, Robert J., Colditz, Graham A., Cole, Kristina, Collins, Natalie, Contrepois, Kevin, Coussens, Lisa M., Creason, Allison L., Crichton, Daniel, Curtis, Christina, Davidsen, Tanja, Davies, Sherri R., de Bruijn, Ino, Dellostritto, Laura, De Marzo, Angelo, Demir, Emek, DeNardo, David G., Diep, Dinh, Ding, Li, Diskin, Sharon, Doan, Xengie, Drewes, Julia, Dubinett, Stephen, Dyer, Michael, Egger, Jacklynn, Eng, Jennifer, Engelhardt, Barbara, Erwin, Graham, Esplin, Edward D., Esserman, Laura, Felmeister, Alex, Feiler, Heidi S., Fields, Ryan C., Fisher, Stephen, Flaherty, Keith, Flournoy, Jennifer, Ford, James M., Fortunato, Angelo, Frangieh, Allison, Frye, Jennifer L., Fulton, Robert S., Galipeau, Danielle, Gan, Siting, Gao, Jianjiong, Gao, Long, Gao, Peng, Gao, Vianne R., Geiger, Tim, George, Ajit, Getz, Gad, Ghosh, Sharmistha, Giannakis, Marios, Gibbs, David L., Gillanders, William E., Goecks, Jeremy, Goedegebuure, Simon P., Gould, Alanna, Gowers, Kate, Gray, Joe W., Greenleaf, William, Gresham, Jeremy, Guerriero, Jennifer L., Guha, Tuhin K., Guimaraes, Alexander R., Guinney, Justin, Gutman, David, Hacohen, Nir, Hanlon, Sean, Hansen, Casey R., Harismendy, Olivier, Harris, Kathleen A., Hata, Aaron, Hayashi, Akimasa, Heiser, Cody, Helvie, Karla, Herndon, John M., Hirst, Gilliam, Hodi, Frank, Hollmann, Travis, Horning, Aaron, Hsieh, James J., Hughes, Shannon, Huh, Won Jae, Hunger, Stephen, Hwang, Shelley E., Iacobuzio-Donahue, Christine A., Ijaz, Heba, Izar, Benjamin, Jacobson, Connor A., Janes, Samuel, Jané-Valbuena, Judit, Jayasinghe, Reyka G., Jiang, Lihua, Johnson, Brett E., Johnson, Bruce, Ju, Tao, Kadara, Humam, Kaestner, Klaus, Kagan, Jacob, Kalinke, Lukas, Keith, Robert, Khan, Aziz, Kibbe, Warren, Kim, Albert H., Kim, Erika, Kim, Junhyong, Kolodzie, Annette, Kopytra, Mateusz, Kotler, Eran, Krueger, Robert, Krysan, Kostyantyn, Kundaje, Anshul, Ladabaum, Uri, Lake, Blue B., Lam, Huy, Laquindanum, Rozelle, Lau, Ken S., Laughney, Ashley M., Lee, Hayan, Lenburg, Marc, Leonard, Carina, Leshchiner, Ignaty, Levy, Rochelle, Li, Jerry, Lian, Christine G., Lim, Kian-Huat, Lin, Jia-Ren, Lin, Yiyun, Liu, Qi, Liu, Ruiyang, Lively, Tracy, Longabaugh, William J.R., Longacre, Teri, Ma, Cynthia X., Macedonia, Mary Catherine, Madison, Tyler, Maher, Christopher A., Maitra, Anirban, Makinen, Netta, Makowski, Danika, Maley, Carlo, Maliga, Zoltan, Mallo, Diego, Maris, John, Markham, Nick, Marks, Jeffrey, Martinez, Daniel, Mashl, Robert J., Masilionais, Ignas, Mason, Jennifer, Massagué, Joan, Massion, Pierre, Mattar, Marissa, Mazurchuk, Richard, Mazutis, Linas, Mazzilli, Sarah A., McKinley, Eliot T., McMichael, Joshua F., Merrick, Daniel, Meyerson, Matthew, Miessner, Julia R., Mills, Gordon B., Mills, Meredith, Mondal, Suman B., Mori, Motomi, Mori, Yuriko, Moses, Elizabeth, Mosse, Yael, Muhlich, Jeremy L., Murphy, George F., Navin, Nicholas E., Nawy, Tal, Nederlof, Michel, Ness, Reid, Nevins, Stephanie, Nikolov, Milen, Nirmal, Ajit Johnson, Nolan, Garry, Novikov, Edward, Oberdoerffer, Philipp, O’Connell, Brendan, Offin, Michael, Oh, Stephen T., Olson, Anastasiya, Ooms, Alex, Ossandon, Miguel, Owzar, Kouros, Parmar, Swapnil, Patel, Tasleema, Patti, Gary J., Pe’er, Dana, Pe'er, Itsik, Peng, Tao, Persson, Daniel, Petty, Marvin, Pfister, Hanspeter, Polyak, Kornelia, Pourfarhangi, Kamyar, Puram, Sidharth V., Qiu, Qi, Quintanal-Villalonga, Álvaro, Raj, Arjun, Ramirez-Solano, Marisol, Rashid, Rumana, Reeb, Ashley N., Regev, Aviv, Reid, Mary, Resnick, Adam, Reynolds, Sheila M., Riesterer, Jessica L., Rodig, Scott, Roland, Joseph T., Rosenfield, Sonia, Rotem, Asaf, Roy, Sudipta, Rozenblatt-Rosen, Orit, Rudin, Charles M., Ryser, Marc D., Santagata, Sandro, Santi-Vicini, Maria, Sato, Kazuhito, Schapiro, Denis, Schrag, Deborah, Schultz, Nikolaus, Sears, Cynthia L., Sears, Rosalie C., Sen, Subrata, Sen, Triparna, Shalek, Alex, Sheng, Jeff, Sheng, Quanhu, Shoghi, Kooresh I., Shrubsole, Martha J., Shyr, Yu, Sibley, Alexander B., Siex, Kiara, Simmons, Alan J., Singer, Dinah S., Sivagnanam, Shamilene, Slyper, Michal, Snyder, Michael P., Sokolov, Artem, Song, Sheng-Kwei, Sorger, Peter K., Southard-Smith, Austin, Spira, Avrum, Srivastava, Sudhir, Stein, Janet, Storm, Phillip, Stover, Elizabeth, Strand, Siri H., Su, Timothy, Sudar, Damir, Sullivan, Ryan, Surrey, Lea, Suvà, Mario, Tan, Kai, Terekhanova, Nadezhda V., Ternes, Luke, Thammavong, Lisa, Thibault, Guillaume, Thomas, George V., Thorsson, Vésteinn, Todres, Ellen, Tran, Linh, Tyler, Madison, Uzun, Yasin, Vachani, Anil, Van Allen, Eliezer, Vandekar, Simon, Veis, Deborah J., Vigneau, Sébastien, Vossough, Arastoo, Waanders, Angela, Wagle, Nikhil, Wang, Liang-Bo, Wendl, Michael C., West, Robert, Williams, Elizabeth H., Wu, Chi-yun, Wu, Hao, Wu, Hung-Yi, Wyczalkowski, Matthew A., Xie, Yubin, Yang, Xiaolu, Yapp, Clarence, Yu, Wenbao, Yuan, Yinyin, Zhang, Dadong, Zhang, Kun, Zhang, Mianlei, Zhang, Nancy, Zhang, Yantian, Zhao, Yanyan, Zhou, Daniel Cui, Zhou, Zilu, Zhu, Houxiang, Zhu, Qin, Zhu, Xiangzhu, Zhu, Yuankun, Zhuang, Xiaowei, Hupalowska, Anna, Rood, Jennifer E., Hanlon, Sean E., Hughes, Shannon K., Hwang, E. Shelley, Johnson, Bruce E., Shalek, Alex K., Spira, Avrum E., and West, Robert B.

Published
2020
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28. Mapping human tissues with highly multiplexed RNA in situ hybridization

Author

Kalhor, Kian, primary, Chen, Chien-Ju, additional, Lee, Ho Suk, additional, Cai, Matthew, additional, Nafisi, Mahsa, additional, Que, Richard, additional, Palmer, Carter R., additional, Yuan, Yixu, additional, Zhang, Yida, additional, Li, Xuwen, additional, Song, Jinghui, additional, Knoten, Amanda, additional, Lake, Blue B., additional, Gaut, Joseph P., additional, Keene, C. Dirk, additional, Lein, Ed, additional, Kharchenko, Peter V., additional, Chun, Jerold, additional, Jain, Sanjay, additional, Fan, Jian-Bing, additional, and Zhang, Kun, additional

Published
2024
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29. The Homeobox Transcription Factor RHOX10 Drives Mouse Spermatogonial Stem Cell Establishment

Author

Song, Hye-Won, Bettegowda, Anilkumar, Lake, Blue B, Zhao, Adrienne H, Skarbrevik, David, Babajanian, Eric, Sukhwani, Meena, Shum, Eleen Y, Phan, Mimi H, Plank, Terra-Dawn M, Richardson, Marcy E, Ramaiah, Madhuvanthi, Sridhar, Vaishnavi, de Rooij, Dirk G, Orwig, Kyle E, Zhang, Kun, and Wilkinson, Miles F

Subjects
Biochemistry and Cell Biology, Bioinformatics and Computational Biology, Biological Sciences, Stem Cell Research, Genetics, Stem Cell Research - Nonembryonic - Non-Human, Regenerative Medicine, Contraception/Reproduction, Biotechnology, 2.1 Biological and endogenous factors, Adult Germline Stem Cells, Animals, Gene Expression Regulation, Developmental, Genes, Developmental, Genes, X-Linked, Homeodomain Proteins, Male, Mice, Mice, Knockout, Multigene Family, Protein Isoforms, Sequence Analysis, RNA, Single-Cell Analysis, Spermatogenesis, Spermatogonia, Rhox, germ cell, germ line stem cell, gonocytes, homeobox, prospermatogonia, spermatogenesis, spermatogonia, spermatogonial stem cells, transcription factor, Medical Physiology, Biological sciences
Abstract

The developmental origins of most adult stem cells are poorly understood. Here, we report the identification of a transcription factor-RHOX10-critical for the initial establishment of spermatogonial stem cells (SSCs). Conditional loss of the entire 33-gene X-linked homeobox gene cluster that includes Rhox10 causes progressive spermatogenic decline, a phenotype indistinguishable from that caused by loss of only Rhox10. We demonstrate that this phenotype results from dramatically reduced SSC generation. By using a battery of approaches, including single-cell-RNA sequencing (scRNA-seq) analysis, we show that Rhox10 drives SSC generation by promoting pro-spermatogonia differentiation. Rhox10 also regulates batteries of migration genes and promotes the migration of pro-spermatogonia into the SSC niche. The identification of an X-linked homeobox gene that drives the initial generation of SSCs has implications for the evolution of X-linked gene clusters and sheds light on regulatory mechanisms influencing adult stem cell generation in general.

Published
2016

30. Neuronal subtypes and diversity revealed by single-nucleus RNA sequencing of the human brain

Author

Lake, Blue B, Ai, Rizi, Kaeser, Gwendolyn E, Salathia, Neeraj S, Yung, Yun C, Liu, Rui, Wildberg, Andre, Gao, Derek, Fung, Ho-Lim, Chen, Song, Vijayaraghavan, Raakhee, Wong, Julian, Chen, Allison, Sheng, Xiaoyan, Kaper, Fiona, Shen, Richard, Ronaghi, Mostafa, Fan, Jian-Bing, Wang, Wei, Chun, Jerold, and Zhang, Kun

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Biomedical and Clinical Sciences, Genetics, Neurosciences, Physical Sciences, Brain Disorders, Human Genome, 1.1 Normal biological development and functioning, Neurological, Cell Nucleus, Cerebral Cortex, Gene Expression Profiling, Humans, Neurons, Sequence Analysis, RNA, Transcriptome, General Science & Technology
Abstract

The human brain has enormously complex cellular diversity and connectivities fundamental to our neural functions, yet difficulties in interrogating individual neurons has impeded understanding of the underlying transcriptional landscape. We developed a scalable approach to sequence and quantify RNA molecules in isolated neuronal nuclei from a postmortem brain, generating 3227 sets of single-neuron data from six distinct regions of the cerebral cortex. Using an iterative clustering and classification approach, we identified 16 neuronal subtypes that were further annotated on the basis of known markers and cortical cytoarchitecture. These data demonstrate a robust and scalable method for identifying and categorizing single nuclear transcriptomes, revealing shared genes sufficient to distinguish previously unknown and orthologous neuronal subtypes as well as regional identity and transcriptomic heterogeneity within the human brain.

Published
2016

31. The chromatin landscape of healthy and injured cell types in the human kidney

Author

Gisch, Debora L. (author), Brennan, Michelle (author), Lake, Blue B. (author), Basta, Jeannine (author), Keller, Mark S. (author), P. Gonçalves, Joana (author), Migas, L.G. (author), Van de Plas, Raf (author), Lardenoije, R. (author), Gisch, Debora L. (author), Brennan, Michelle (author), Lake, Blue B. (author), Basta, Jeannine (author), Keller, Mark S. (author), P. Gonçalves, Joana (author), Migas, L.G. (author), Van de Plas, Raf (author), and Lardenoije, R. (author)

Abstract

There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidney’s active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we note distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3, KLF6, and KLF10 regulates the transition between health and injury, while in thick ascending limb cells this transition is regulated by NR2F1. Further, combined perturbation of ELF3, KLF6, and KLF10 distinguishes two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks., Pattern Recognition and Bioinformatics, Team Raf Van de Plas

Published
2024
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32. Protein N-Glycans in Healthy and Sclerotic Glomeruli in Diabetic Kidney Disease

Author

Veličković, Dušan, Shapiro, John P., Parikh, Samir V., Rovin, Brad, Toto, Robert D., Vazquez, Miguel A., Poggio, Emilio D., O'Toole, John F., Sedor, John R., Alexandrov, Theodore, Jain, Sanjay, Bitzer, Markus, Hodgin, Jeffrey, Veličković, Marija, Sharma, Kumar, Anderton, Christopher R., Adeyi, Oyedele A., Alakwaa, Fadhl, Alexandrov, Theodore, Allen, Jamie L., Alpers, Charles E., Alvear, Alison Bunio, Ambekar, Akhil, Ancheta, Joed, Anderton, Christopher R., Angus, Sophia A., Anjani, Kavya, Appelbaum, Paul S., Ardayfio, Joseph, Arora, Tanima, Ascani, Heather K., Asghari, Mahla, El-Achkar, Tarek M., Athar, Humra, Atta, Mohamed G., Aulisio, Mark P., Aw, Stephanie J., Azeloglu, Evren U., Bagne, Cathy A., Balderes, Olivia, Balis, Ulysses G.J., Barasch, Jonathan, Barisoni, Laura, Barwinska, Daria, Basta, Jeannine, Bebiak, Jack, Beck, Laurence H., Berge, Jerica M., Berglund, Ashley C., Bernard, Lauren, Berry, Brooke, Beyda, David H., Bhanushali, Jini Ashok, Bitzer, Markus, Bjornstad, Petter, Blanc, Victoria M., Blank, Kristina N., Bledsoe, Sharon B., Bogen, Steve, Bomback, Andrew S., Bonevich, Nikole, Border, Samuel, Börner, Katy, Bowen, William S., Boys, Charlotte, Bracamonte, Erika R., Bream, Peter R., Brosius, Frank C., Brown, Keith D., Budiman, Tifanny, Bueckle, Andreas, Bui, J.T., James, T., Burg, Ashley R., Burgess, Adam, Bush, Lakeshia, Bush, William S., Cai, Qi, Calixte, Marie Florence, Cameron-Wheeler, Tashas, Campbell, Kirk N, Campbell, Taneisha, Campbell, Catherine, Campos, Baltazar, Canetta, Pietro A., Cantley, Lloyd G, Caramori, M. Luiza, Carmona-Powell, Eunice, Carson, Jonas M, Chan, Lili, Chen, Sarah W, Chen, Yijiang, Cheng, Ying-Hua, Bejarano, Maria Chilo, Choe, Kisurb, Cimino, James G., Coca, Steven G., Coleman, Alyson, Colley, Madeline E., Collie, Mary M., Colona, Mia R., Commander, Clayton W., Conlon, Kristine, Conser, Ninive, Cooperman, Leslie, Corona-Villalobos, Celia P., Crawford, Dana C., Creger, Nathan, Cuevas-Rios, Yarieli, D'Agati, Vivette ., Dagher, Pierre c., de Boer, Ian H., de Caestecker, M.P, de Cos, Marina, Gonçalves, Joana P., Dekker, Matthew, Demeke, Dawit, Dighe, Ashveena L, Ding, Yanli, Djambazova, Katerina V., Donohoe, Isabel, Dowd, Frederick, Drawz, P.E., Dufresne, Martin, Dull, Rachel, Dunn, Kenneth W., Duran, Daniel Damian, Eadon, Michael T, Eddy, Sean, Elder, Michele M, Fallegger, Robin, Farrow, Melissa A, Ferkowicz, Michael, Fine, Derek M., Flanagan, Siobhan M., Fogo, Agnes B., Fox, Monica L., Frey, Renee, Froment, Anne, Gaba, Ron C., Gadegbeku, Crystal A, Gaut, Joseph P., Gehlenborg, Nils, Geraghty, Molly C, Ghag, Reetika, Gilliam, Matthew, Ginley, Brandon, Gisch, Debora, Gordon, Ronald E., Gorman, Brittney L., Greka, Anna, Grewenow, Stephanie M., Gurung, Bhupendra Kumar, Guthrie, Leah, Hacohen, Nir, Haddad, Samuel, Hall, Daniel E., Hansen, Jens, Harindhanavudhi, Tasma, Hartman, John, Hayashi, Lynda, Haydak, Jonathan, He, John Cijiang, He, Yongqun, Hedayati, S. Susan, Henderson, Dori, Henderson, Joel M, Hendricks, Allen R, Henshaw, Asari, Herlitz, Leal, Hernandez, Jeanine, Herr, Bruce W., Himmelfarb, Jonathan, Hodgin, Jeffrey B., Hoofnagle, Andrew N, Horowitz, Carol R., Hsieh, E.W.Y., Huynh, Courtney, Iyengar, Ravi, Jain, Sanjay, Janowczyk, Andrew, Jeffers, Vivian, Jefferson, Nichole M., Jennette, J Charles, Johansen, Camille, Jolly, Stacey, Jones, Christopher J., Jones, Jennifer L., Jones, Kiasha, Joyeux, Cienn N., Ju, Wenjun, Judd, Audra M., Kakade, Vijayakumar R, Kakarla, Dhatri, Kaspari, Rachel R., Kaushal, Madhurima, Keefe, Nicole, Keller, Mark S., Kelley, Sara S., Kellum, John A., Kelly, K. J., Kelly, Tanika N., Kermani, Asra, Kiryluk, Krzysztof, Klett, Susan, Knight, Richard A., Knoten, Amanda, Koch, Gina, Koewler, Robert, Kretzler, Matthias, Kruse, Angela R.S., Küchenhoff, Leonie, Lake, Blue B., Lardenoije, Roy, Larson, Astrid, Larson, Brandon G, Lash, James P., Laszik, Zoltan G., Lecker, Stewart H., Lee, Simon C., Lee, Sora, Lefferts, Sean, Li, Xiang, Lienczewski, Chrysta C, Limonte, Christine P, Lucarelli, Nicholas, Lukowski, Jessica, Lutnick, Brendon, Ma, Shihong, Ma, Sisi, Madabhushi, Anant, Maikhor, Shana, Mao, Weiguang, Mariani, Laura H., Markovic, Marina, Marquez, Nicole, Marshall, Jamie L., McAdams, Meredith C, McClelland, Robyn L., McCown, Phillip J., McMahon, Gearoid Michael, McMurray, Amy, Mehl, Karla, Meliambro, Kristin, Ferreira, Ricardo Melo, Mendoza, Katherine, Menez, Steven, Menon, Rajasree, Meza, Natalie, Migas, Lukasz G., Miller, R. Tyler, Mimar, Sayat, Minor, Brittany C, Mody, Priya, Moeckel, Gilbert W., Moledina, D.G., Molina-Guzman, Jenny, Monroy-Trujillo, Jose M, Morales, Alexander, Moreno, Vanessa, Mottl, Amy K., Mukatash, Tariq, Munar, Dane, Murugan, Raghavan, Nachman, Patrick H., Nadkarni, Girish N, Naglah, Ahmed, Nair, Viji, Nam, Yunbi, Narasimhan, R., Nwanne, Gerald, O'Malley, Charles, O'Toole, John F., Toro, Fernanda Ochoa, Oliver, George (Holt), Onul, Ingrid F, Otto, Edgar A., Palevsky, Paul M., Palmer, Ellen, Pamreddy, Annapurna, Parikh, Chirag R., Parikh, Samir V, Park, Christopher, Park, Harold, Paša-Tolić, Ljiljana, Patel, Jiten, Patel, Marissa, Patlis, Boris S., Paul, Anindya S., Phuong, Jimmy, Pillai, Anil, Pinkeney, Roy, Plisiewicz, Alexa, Poggio, Emilio D, Pollack, Ari, Prasad, Pottumarthi V, Pyle, Laura, Quardokus, Ellen M., Quiroga, Arabela, Ragi, Nagarjunachary, Randhawa, Parmjeet, Randle, Teresa, Rao, Via, Rauchman, Michael, Rauwolf, Nicolas J, Reamy, Rebecca, Record, Elizabeth G., Redmond, Devona, Rennke, Helmut, Renteria, Amada, Rezaei, Kasra A, Rhodes, Rosamond, Ricardo, Ana C., Rice, Samuel, Rivera, Marcelino, Roberts, Glenda V., Rosas, R., Sylvia, E., Rose, Michael P., Rosen, Seymour, Rosenberg, Avi Z., Rosenberg, Michael S., Rosengart, Matthew R., Rovin, Brad H., Roy, Neil, Roy-Chaudhury, Prabir, Rubinsky, Melissa D., Sabo, Angela R., Saez-Rodriguez, Julio, Safadi, Sami, Samari, Imane H., Sanora, Ana Celina, Sarder, Pinaki, Sarkisova, Natalya, Sarwal, Minnie M, Saul, John, Saunders, Milda R., Schaub, Jennifer A., Schmidt, IM, Scott, Raymond, Scroggins, Aaron, Sealfon, Rachel S. G., Sedor, John R., Sendrey, Dianna, Setty, Suman, Shah, Sonya, Shariff, Saad Mohammed, Sharma, Kumar, Shaw, Melissa M., Sigdel, Tara K, Silva, Paolo S., Snyder, Jaime, Snyder, Michelle L., Spates-Harden, Kassandra, Sperati, C. John, Spraggins, Jeffrey M., Srivastava, Anand, Stashevsky, Jennifer, Steck, Becky, Stillman, Isaac E, Stutzke, Christy, Subramanian, Lalita, Sun, Jennifer K., Rajan, Sandhya Sundar, Sutton, Timothy A., Taliercio, Jonathan J, Tan, Roderick, Tanevski, Jovan, Thajudeen, Bijin, Thurman, Joshua M., Tokita, Joji, Torrealba, Jose R., Toto, Robert D, Tout, Haneen, Troyanskaya, Olga G, Tsosie, Rebecca, Turner, Jeffrey M, Tuttle, Katherine R., Ugwuowo, Ugochukwu, Upadhyay, Ashish, Valerius, M. Todd, Van de Plas, Raf, Varela, German, Vazquez, Miguel A., Velickovic, Dusan, Venkatachalam, Manjeri, Verdoes, Abraham, Verma, Ashish, Victoria-Castro, Angela M., Vijayan, Anitha, Villalobos, Alexander, Viloria, Noralinda B., Vinovskis, Carissa, Vita, Tina, Waikar, Sushrut S., Wang, Ashley R., Wang, Bangchen, Wang, Nancy, Wang, Ruikang, Wangperawong, Artit, Ward, Stephen C, Warfield, Curtis, Weins, Astrid, Wen, Natasha, Wen, Yumeng, Wilcox, Adam, Williams, James C., Williams, Kayleen, Williams, Mark E., Wilson, F. Perry, Winfree, Seth, Winters, James, Wofford, Stephanie, Wolf, Susan M., Wong, Aaron, Woodhead, Gregory, Wright, Devin M., Wright, Zach, Wright, Zoe, Wrobel, Julia, Xing, Fuyong, Xu, Alan, Yadati, Pranav, Ye, Hongping, Young, Bessie A., Yu, Guanghao, Mon-Wei Yu, Samuel, Zeinoun, Gabriel, Zeitler, Evan M., Zhang, Bo, Zhang, Guanshi, and Zhang, Yi

Published
2024
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33. Fluid Dynamics of Stellar Jets in Real Time: Third Epoch HST Images of HH 1, HH 34, and HH 47

Author

Hartigan, P., Frank, A., Foster, J. M., Wilde, B. H., Douglas, M., Rosen, P. A., Coker, R. F., Blue, B. E., and Hansen, J. F.

Subjects
Astrophysics - Solar and Stellar Astrophysics, Astrophysics - Astrophysics of Galaxies
Abstract

We present new, third-epoch HST H-alpha and [S II] images of three HH jets (HH 1 and 2, HH 34, and HH 47) and compare these images with those from the previous epochs. The high-spatial resolution, coupled with a time-series whose cadence is of order both the hydrodynamical and radiative cooling timescales of the flow allows us to follow the hydrodynamical/magnetohydrodynamical evolution of an astrophysical plasma system in which ionization and radiative cooling play significant roles. Cooling zones behind the shocks are resolved, so it is possible to identify which way material flows through a given shock wave. The images show that heterogeneity is paramount in these jets, with clumps dominating the morphologies of both bow shocks and their Mach disks. This clumpiness exists on scales smaller than the jet widths and determines the behavior of many of the features in the jets. Evidence also exists for considerable shear as jets interact with their surrounding molecular clouds, and in several cases we observe shock waves as they form and fade where material emerges from the source and as it proceeds along the beam of the jet. Fine-structure within two extended bow shocks may result from Mach stems that form at the intersection points of oblique shocks within these clumpy objects. Taken together, these observations represent the most significant foray thus far into the time domain for stellar jets, and comprise one of the richest data sets in existence for comparing the behavior of a complex astrophysical plasma flows with numerical simulations and laboratory experiments., Comment: 17 figures. High-resolution PDF with better figure quality available at http://sparky.rice.edu/~hartigan/pub.html

Published
2011
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34. Laboratory Experiments, Numerical Simulations, and Astronomical Observations of Deflected Supersonic Jets: Application to HH 110

Author

Hartigan, P., Foster, J. M., Wilde, B. H., Coker, R. F., Rosen, P. A., Hansen, J. F., Blue, B. E., Williams, R. J. R., Carver, R., and Frank, A.

Subjects
Astrophysics - Astrophysics of Galaxies, Astrophysics - Instrumentation and Methods for Astrophysics
Abstract

Collimated supersonic flows in laboratory experiments behave in a similar manner to astrophysical jets provided that radiation, viscosity, and thermal conductivity are unimportant in the laboratory jets, and that the experimental and astrophysical jets share similar dimensionless parameters such as the Mach number and the ratio of the density between the jet and the ambient medium. Laboratory jets can be studied for a variety of initial conditions, arbitrary viewing angles, and different times, attributes especially helpful for interpreting astronomical images where the viewing angle and initial conditions are fixed and the time domain is limited. Experiments are also a powerful way to test numerical fluid codes in a parameter range where the codes must perform well. In this paper we combine images from a series of laboratory experiments of deflected supersonic jets with numerical simulations and new spectral observations of an astrophysical example, the young stellar jet HH 110. The experiments provide key insights into how deflected jets evolve in 3-D, particularly within working surfaces where multiple subsonic shells and filaments form, and along the interface where shocked jet material penetrates into and destroys the obstacle along its path. The experiments also underscore the importance of the viewing angle in determining what an observer will see. The simulations match the experiments so well that we can use the simulated velocity maps to compare the dynamics in the experiment with those implied by the astronomical spectra. The experiments support a model where the observed shock structures in HH 110 form as a result of a pulsed driving source rather than from weak shocks that may arise in the supersonic shear layer between the Mach disk and bow shock of the jet's working surface., Comment: Full resolution figures available at http://sparky.rice.edu/~hartigan/pub.html To appear in ApJ

Published
2009
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35. Author Correction: Comparative cellular analysis of motor cortex in human, marmoset and mouse

Author

Bakken, Trygve E., Jorstad, Nikolas L., Hu, Qiwen, Lake, Blue B., Tian, Wei, Kalmbach, Brian E., Crow, Megan, Hodge, Rebecca D., Krienen, Fenna M., Sorensen, Staci A., Eggermont, Jeroen, Yao, Zizhen, Aevermann, Brian D., Aldridge, Andrew I., Bartlett, Anna, Bertagnolli, Darren, Casper, Tamara, Castanon, Rosa G., Crichton, Kirsten, Daigle, Tanya L., Dalley, Rachel, Dee, Nick, Dembrow, Nikolai, Diep, Dinh, Ding, Song-Lin, Dong, Weixiu, Fang, Rongxin, Fischer, Stephan, Goldman, Melissa, Goldy, Jeff, Graybuck, Lucas T., Herb, Brian R., Hou, Xiaomeng, Kancherla, Jayaram, Kroll, Matthew, Lathia, Kanan, van Lew, Baldur, Li, Yang Eric, Liu, Christine S., Liu, Hanqing, Lucero, Jacinta D., Mahurkar, Anup, McMillen, Delissa, Miller, Jeremy A., Moussa, Marmar, Nery, Joseph R., Nicovich, Philip R., Niu, Sheng-Yong, Orvis, Joshua, Osteen, Julia K., Owen, Scott, Palmer, Carter R., Pham, Thanh, Plongthongkum, Nongluk, Poirion, Olivier, Reed, Nora M., Rimorin, Christine, Rivkin, Angeline, Romanow, William J., Sedeño-Cortés, Adriana E., Siletti, Kimberly, Somasundaram, Saroja, Sulc, Josef, Tieu, Michael, Torkelson, Amy, Tung, Herman, Wang, Xinxin, Xie, Fangming, Yanny, Anna Marie, Zhang, Renee, Ament, Seth A., Behrens, M. Margarita, Bravo, Hector Corrada, Chun, Jerold, Dobin, Alexander, Gillis, Jesse, Hertzano, Ronna, Hof, Patrick R., Höllt, Thomas, Horwitz, Gregory D., Keene, C. Dirk, Kharchenko, Peter V., Ko, Andrew L., Lelieveldt, Boudewijn P., Luo, Chongyuan, Mukamel, Eran A., Pinto-Duarte, António, Preiss, Sebastian, Regev, Aviv, Ren, Bing, Scheuermann, Richard H., Smith, Kimberly, Spain, William J., White, Owen R., Koch, Christof, Hawrylycz, Michael, Tasic, Bosiljka, Macosko, Evan Z., McCarroll, Steven A., Ting, Jonathan T., Zeng, Hongkui, Zhang, Kun, Feng, Guoping, Ecker, Joseph R., Linnarsson, Sten, and Lein, Ed S.

Published
2022
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36. Plasma density from Cerenkov radiation, betatron oscillations, and beam steering in a plasma wakefield experiment at 30 GeV

Author

Catravas, P., Chattopadhyay, S., Esarey, E., Leemans, W.P., Assmann, R., Decker, F.-J., Hogan, M.J., Iverson, R., Siemann, R.H., Walz, D., Whittum, D., Blue, B., Clayton, C., Joshi, C., Marsh, K., Mori, W.B., Wang, S., Katsouleas, T., Lee, S., and Muggli, P.

Subjects
Particle accelerators, plasma wakefield acceleration Cerenkov radiation plasma density diagnostic atomic spectral lines
Published
2001

37. Integrated single-cell sequencing and histopathological analyses reveal diverse injury and repair responses in a participant with acute kidney injury: a clinical-molecular-pathologic correlation

Author

Rajasree Menon, Andrew S. Bomback, Blue B. Lake, Christy Stutzke, Stephanie M. Grewenow, Steven Menez, Vivette D. D’Agati, Sanjay Jain, Richard Knight, Stewart H. Lecker, Isaac Stillman, Steve Bogen, Laurence H. Beck, Sushrut Waikar, Gearoid M. McMahon, Astrid Weins, Mia R. Colona, Nir Hacohen, Paul J. Hoover, Mark Aulisio, William S. Bush, Dana C. Crawford, John O'toole, Emilio Poggio, John Sedor, Leslie Cooperman, Stacey Jolly, Leal Herlitz, Jane Nguyen, Agustin Gonzalez-Vicente, Ellen Palmer, Dianna Sendrey, Carissa Vinovskis, Petter M. Bjornstad, Paul Appelbaum, Jonathan M. Barasch, Vivette D. D'Agati, Krzysztof Kiryluk, Karla Mehl, Pietro A. Canetta, Ning Shang, Olivia Balderes, Satoru Kudose, Shweta Bansal, Theodore Alexandrov, Helmut Rennke, Tarek M. El-Achkar, Yinghua Cheng, Pierre C. Dagher, Michael T. Eadon, Kenneth W. Dunn, Katherine J. Kelly, Timothy A. Sutton, Daria Barwinska, Michael J. Ferkowicz, Seth Winfree, Sharon Bledsoe, Marcelino Rivera, James C. Williams, Ricardo Melo Ferreira, Chirag R. Parikh, Celia P. Corona-Villalobos, Avi Rosenberg, Sylvia E. Rosas, Neil Roy, Mark Williams, Evren U. Azeloglu, Cijang He, Ravi Iyengar, Jens Hansen, Yuguang Xiong, Brad Rovin, Samir Parikh, John P. Shapiro, Christopher R. Anderton, Ljiljana Pasa-Tolic, Dusan Velickovic, Jessica Lukowski, George Oliver, Joseph Ardayfio, Jack Bebiak, Keith Brown, Catherine E. Campbell, John Saul, Anna Shpigel, Robert Koewler, Taneisha Campbell, Lynda Hayashi, Nichole Jefferson, Glenda V. Roberts, Roy Pinkeney, Olga Troyanskaya, Rachel Sealfon, Katherine R. Tuttle, Yury Goltsev, Kun Zhang, Zoltan G. Laszik, Garry Nolan, Patrick Boada, Minnie Sarwal, Tara Sigdel, Paul J. Lee, Rita R. Alloway, E. Steve Woodle, Heather Ascani, Ulysses G.J. Balis, Jeffrey B. Hodgin, Matthias Kretzler, Chrysta Lienczewski, Laura H. Mariani, Becky Steck, Yougqun He, Edgar Otto, Jennifer Schaub, Victoria M. Blanc, Sean Eddy, Ninive C. Conser, Jinghui Luo, Paul M. Palevsky, Matthew Rosengart, John A. Kellum, Daniel E. Hall, Parmjeet Randhawa, Mitchell Tublin, Raghavan Murugan, Michele M. Elder, James Winters, Charles E. Alpers, Kristina N. Blank, Jonas Carson, Ian H. De Boer, Ashveena L. Dighe, Jonathan Himmelfarb, Sean D. Mooney, Stuart Shankland, Kayleen Williams, Christopher Park, Frederick Dowd, Robyn L. McClelland, Stephen Daniel, Andrew N. Hoofnagle, Adam Wilcox, Kumar Sharma, Manjeri Venkatachalam, Guanshi Zhang, Annapurna Pamreddy, Hongping Ye, Richard Montellano, Robert D. Toto, Miguel Vazquez, Simon C. Lee, R. Tyler Miller, Orson W. Moe, Jose Torrealba, Nancy Wang, Asra Kermani, Kamalanathan Sambandam, Harold Park, S. Susan Hedayati, Christopher Y. Lu, Anitha Vijayan, Joseph P. Gaut, Dennis Moledina, Francis P. Wilson, Ugochukwu Ugwuowo, and Tanima Arora

Subjects
Pathology, Clinical, Nephrology, Humans, Acute Kidney Injury, Kidney, Article
Published
2022
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41. A reference tissue atlas for the human kidney

Author

Jens, Hansen, Rachel, Sealfon, Rajasree, Menon, Michael T, Eadon, Blue B, Lake, Becky, Steck, Kavya, Anjani, Samir, Parikh, Tara K, Sigdel, Guanshi, Zhang, Dusan, Velickovic, Daria, Barwinska, Theodore, Alexandrov, Dejan, Dobi, Priyanka, Rashmi, Edgar A, Otto, Miguel, Rivera, Michael P, Rose, Christopher R, Anderton, John P, Shapiro, Annapurna, Pamreddy, Seth, Winfree, Yuguang, Xiong, Yongqun, He, Ian H, de Boer, Jeffrey B, Hodgin, Laura, Barisoni, Abhijit S, Naik, Kumar, Sharma, Minnie M, Sarwal, Kun, Zhang, Jonathan, Himmelfarb, Brad, Rovin, Tarek M, El-Achkar, Zoltan, Laszik, John Cijiang, He, Pierre C, Dagher, M Todd, Valerius, Sanjay, Jain, Lisa M, Satlin, Olga G, Troyanskaya, Matthias, Kretzler, Ravi, Iyengar, and Evren U, Azeloglu

Subjects
Proteomics, Multidisciplinary, Humans, Metabolomics, Kidney Diseases, Kidney, Transcriptome
Abstract

Kidney Precision Medicine Project (KPMP) is building a spatially specified human kidney tissue atlas in health and disease with single-cell resolution. Here, we describe the construction of an integrated reference map of cells, pathways, and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 56 adult subjects. We use single-cell/nucleus transcriptomics, subsegmental laser microdissection transcriptomics and proteomics, near-single-cell proteomics, 3D and CODEX imaging, and spatial metabolomics to hierarchically identify genes, pathways, and cells. Integrated data from these different technologies coherently identify cell types/subtypes within different nephron segments and the interstitium. These profiles describe cell-level functional organization of the kidney following its physiological functions and link cell subtypes to genes, proteins, metabolites, and pathways. They further show that messenger RNA levels along the nephron are congruent with the subsegmental physiological activity. This reference atlas provides a framework for the classification of kidney disease when multiple molecular mechanisms underlie convergent clinical phenotypes.

Published
2022
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42. A spatially anchored transcriptomic atlas of the human kidney papilla identifies significant immune injury in patients with stone disease.

Author

Canela, Victor Hugo, Bowen, William S., Ferreira, Ricardo Melo, Syed, Farooq, Lingeman, James E., Sabo, Angela R., Barwinska, Daria, Winfree, Seth, Lake, Blue B., Cheng, Ying-Hua, Gaut, Joseph P., Ferkowicz, Michael, LaFavers, Kaice A., Zhang, Kun, Coe, Fredric L., Worcester, Elaine, the Kidney Precision Medicine Project, Jain, Sanjay, Eadon, Michael T., and Williams Jr., James C.

Subjects
KIDNEY stones, MEDICAL care use, CALCIUM oxalate, TRANSCRIPTOMES, MATRIX metalloproteinases, KIDNEYS
Abstract

Kidney stone disease causes significant morbidity and increases health care utilization. In this work, we decipher the cellular and molecular niche of the human renal papilla in patients with calcium oxalate (CaOx) stone disease and healthy subjects. In addition to identifying cell types important in papillary physiology, we characterize collecting duct cell subtypes and an undifferentiated epithelial cell type that was more prevalent in stone patients. Despite the focal nature of mineral deposition in nephrolithiasis, we uncover a global injury signature characterized by immune activation, oxidative stress and extracellular matrix remodeling. We also identify the association of MMP7 and MMP9 expression with stone disease and mineral deposition, respectively. MMP7 and MMP9 are significantly increased in the urine of patients with CaOx stone disease, and their levels correlate with disease activity. Our results define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human papilla and identify associated urinary biomarkers. Kidney stone disease causes significant morbidity and increases in health care utilization. Here, the authors define the spatial molecular landscape and specific pathways contributing to stone-mediated injury in the human renal papilla and identify associated urinary biomarkers. [ABSTRACT FROM AUTHOR]

Published
2023
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43. A Participant-Centered Approach to Understanding Risks and Benefits of Participation in Research Informed by the Kidney Precision Medicine Project

Author

Butler, Catherine R., primary, Appelbaum, Paul S., additional, Ascani, Heather, additional, Aulisio, Mark, additional, Campbell, Catherine E., additional, de Boer, Ian H., additional, Dighe, Ashveena L., additional, Hall, Daniel E., additional, Himmelfarb, Jonathan, additional, Knight, Richard, additional, Mehl, Karla, additional, Murugan, Raghavan, additional, Rosas, Sylvia E., additional, Sedor, John R., additional, O’Toole, John F., additional, Tuttle, Katherine R., additional, Waikar, Sushrut S., additional, Freeman, Michael, additional, Alexandrov, Theodore, additional, Alpers, Charles E., additional, Anderton, Christopher R., additional, Ardayfio, Joseph, additional, Arora, Tanima, additional, El-Achkar, Tarek M., additional, Azeloglu, Evren U., additional, Balderes, Olivia, additional, Balis, Ulysses G.J., additional, Bansal, Shweta, additional, Barasch, Jonathan M., additional, Barwinska, Daria, additional, Bebiak, Jack, additional, Blanc, Victoria M., additional, Blank, Kristina N., additional, Bomback, Andrew S., additional, Brown, Keith D., additional, Bush, William S., additional, Campbell, Taneisha, additional, Canetta, Pietro A., additional, Carson, Jonas, additional, Cooperman, Leslie, additional, Crawford, Dana C., additional, D’Agati, Vivette D., additional, Dagher, Pierre C., additional, Daniel, Stephen, additional, Dowd, Frederick, additional, Dunn, Kenneth W., additional, Eadon, Michael T., additional, Eddy, Sean, additional, Elder, Michele M., additional, Ferkowicz, Michael J., additional, Gaut, Joe P., additional, Goltsev, Yury, additional, Gonzalez-Vicente, Agustin, additional, Hacohen, Nir, additional, Hansen, Jens, additional, Hayashi, Lynda, additional, He, Oliver, additional, He, Cijang, additional, Hedayati, S. Susan, additional, Herlitz, Leal, additional, Hodgin, Jeffrey B., additional, Hoofnagle, Andrew N., additional, Hoover, Paul J., additional, Iyengar, Ravi, additional, Jain, Sanjay, additional, Jefferson, Nichole, additional, Jolly, Stacey, additional, Kellum, John A., additional, Kelly, Katherine J., additional, Kermani, Asra, additional, Kiryluk, Krzysztof, additional, Koewler, Robert, additional, Kretzler, Matthias, additional, Lake, Blue B., additional, Laszik, Zoltan G., additional, Lecker, Stewart H., additional, Lee, Simon C., additional, Lienczewski, Chrysta, additional, Lu, Christopher Y., additional, Mariani, Laura H., additional, McClelland, Robyn L., additional, McMahon, Gearoid M., additional, Menez, Steven, additional, Menon, Rajasree, additional, Miller, Tyler, additional, Moe, Orson W., additional, Moledina, Dennis, additional, Mooney, Sean D., additional, Nguyen, Jane, additional, Nolan, Garry, additional, Oliver, George, additional, Otto, Edgar, additional, Palevsky, Paul M., additional, Palmer, Ellen, additional, Pamreddy, Annapurna, additional, Parikh, Chirag R., additional, Parikh, Samir, additional, Park, Christopher, additional, Park, Harold, additional, Pasa-Tolic, Ljiljana, additional, Pinkeney, Roy, additional, Poggio, Emilio, additional, Randhawa, Parmjeet, additional, Rennke, Helmut, additional, Roberts, Glenda V., additional, Rosenberg, Avi, additional, Rosengart, Matthew, additional, Rovin, Brad, additional, Roy, Neil, additional, Sambandam, Kamalanathan, additional, Sarwal, Minnie, additional, Saul, John, additional, Schaub, Jennifer, additional, Sealfon, Rachel, additional, Shang, Ning, additional, Shankland, Stuart, additional, Sharma, Kumar, additional, Shpigel, Anna, additional, Sigdel, Tara, additional, Steck, Becky, additional, Stillman, Isaac, additional, Stutzke, Edith Christine, additional, Sutton, Timothy A., additional, Torrealba, Jose, additional, Toto, Robert D., additional, Troyanskaya, Olga, additional, Tublin, Mitchell, additional, Ugwuowo, Ugochukwu, additional, Vazquez, Miguel, additional, Velickovic, Dusan, additional, Venkatachalam, Manjeri, additional, Vijayan, Anitha, additional, Corona-Villalobos, Celia P., additional, Wang, Nancy, additional, Weins, Astrid, additional, Wilcox, Adam, additional, Williams, Kayleen, additional, Williams, Mark, additional, Wilson, Francis P., additional, Winfree, Seth, additional, Xiong, Yuguang, additional, Zhang, Kun, additional, and Zhang, Guanshi, additional

Published
2022
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44. Integrated single-cell sequencing and histopathological analyses reveal diverse injury and repair responses in a participant with acute kidney injury: a clinical-molecular-pathologic correlation

Author

Menon, Rajasree, primary, Bomback, Andrew S., additional, Lake, Blue B., additional, Stutzke, Christy, additional, Grewenow, Stephanie M., additional, Menez, Steven, additional, D’Agati, Vivette D., additional, Jain, Sanjay, additional, Knight, Richard, additional, Lecker, Stewart H., additional, Stillman, Isaac, additional, Bogen, Steve, additional, Beck, Laurence H., additional, Waikar, Sushrut, additional, McMahon, Gearoid M., additional, Weins, Astrid, additional, Colona, Mia R., additional, Hacohen, Nir, additional, Hoover, Paul J., additional, Aulisio, Mark, additional, Bush, William S., additional, Crawford, Dana C., additional, O'toole, John, additional, Poggio, Emilio, additional, Sedor, John, additional, Cooperman, Leslie, additional, Jolly, Stacey, additional, Herlitz, Leal, additional, Nguyen, Jane, additional, Gonzalez-Vicente, Agustin, additional, Palmer, Ellen, additional, Sendrey, Dianna, additional, Vinovskis, Carissa, additional, Bjornstad, Petter M., additional, Appelbaum, Paul, additional, Barasch, Jonathan M., additional, D'Agati, Vivette D., additional, Kiryluk, Krzysztof, additional, Mehl, Karla, additional, Canetta, Pietro A., additional, Shang, Ning, additional, Balderes, Olivia, additional, Kudose, Satoru, additional, Bansal, Shweta, additional, Alexandrov, Theodore, additional, Rennke, Helmut, additional, El-Achkar, Tarek M., additional, Cheng, Yinghua, additional, Dagher, Pierre C., additional, Eadon, Michael T., additional, Dunn, Kenneth W., additional, Kelly, Katherine J., additional, Sutton, Timothy A., additional, Barwinska, Daria, additional, Ferkowicz, Michael J., additional, Winfree, Seth, additional, Bledsoe, Sharon, additional, Rivera, Marcelino, additional, Williams, James C., additional, Ferreira, Ricardo Melo, additional, Parikh, Chirag R., additional, Corona-Villalobos, Celia P., additional, Rosenberg, Avi, additional, Rosas, Sylvia E., additional, Roy, Neil, additional, Williams, Mark, additional, Azeloglu, Evren U., additional, He, Cijang, additional, Iyengar, Ravi, additional, Hansen, Jens, additional, Xiong, Yuguang, additional, Rovin, Brad, additional, Parikh, Samir, additional, Shapiro, John P., additional, Anderton, Christopher R., additional, Pasa-Tolic, Ljiljana, additional, Velickovic, Dusan, additional, Lukowski, Jessica, additional, Oliver, George, additional, Ardayfio, Joseph, additional, Bebiak, Jack, additional, Brown, Keith, additional, Campbell, Catherine E., additional, Saul, John, additional, Shpigel, Anna, additional, Koewler, Robert, additional, Campbell, Taneisha, additional, Hayashi, Lynda, additional, Jefferson, Nichole, additional, Roberts, Glenda V., additional, Pinkeney, Roy, additional, Troyanskaya, Olga, additional, Sealfon, Rachel, additional, Tuttle, Katherine R., additional, Goltsev, Yury, additional, Zhang, Kun, additional, Laszik, Zoltan G., additional, Nolan, Garry, additional, Boada, Patrick, additional, Sarwal, Minnie, additional, Sigdel, Tara, additional, Lee, Paul J., additional, Alloway, Rita R., additional, Woodle, E. Steve, additional, Ascani, Heather, additional, Balis, Ulysses G.J., additional, Hodgin, Jeffrey B., additional, Kretzler, Matthias, additional, Lienczewski, Chrysta, additional, Mariani, Laura H., additional, Menon, Rajasree, additional, Steck, Becky, additional, He, Yougqun, additional, Otto, Edgar, additional, Schaub, Jennifer, additional, Blanc, Victoria M., additional, Eddy, Sean, additional, Conser, Ninive C., additional, Luo, Jinghui, additional, Palevsky, Paul M., additional, Rosengart, Matthew, additional, Kellum, John A., additional, Hall, Daniel E., additional, Randhawa, Parmjeet, additional, Tublin, Mitchell, additional, Murugan, Raghavan, additional, Elder, Michele M., additional, Winters, James, additional, Alpers, Charles E., additional, Blank, Kristina N., additional, Carson, Jonas, additional, De Boer, Ian H., additional, Dighe, Ashveena L., additional, Himmelfarb, Jonathan, additional, Mooney, Sean D., additional, Shankland, Stuart, additional, Williams, Kayleen, additional, Park, Christopher, additional, Dowd, Frederick, additional, McClelland, Robyn L., additional, Daniel, Stephen, additional, Hoofnagle, Andrew N., additional, Wilcox, Adam, additional, Sharma, Kumar, additional, Venkatachalam, Manjeri, additional, Zhang, Guanshi, additional, Pamreddy, Annapurna, additional, Ye, Hongping, additional, Montellano, Richard, additional, Toto, Robert D., additional, Vazquez, Miguel, additional, Lee, Simon C., additional, Miller, R. Tyler, additional, Moe, Orson W., additional, Torrealba, Jose, additional, Wang, Nancy, additional, Kermani, Asra, additional, Sambandam, Kamalanathan, additional, Park, Harold, additional, Hedayati, S. Susan, additional, Lu, Christopher Y., additional, Vijayan, Anitha, additional, Gaut, Joseph P., additional, Moledina, Dennis, additional, Wilson, Francis P., additional, Ugwuowo, Ugochukwu, additional, and Arora, Tanima, additional

Published
2022
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46. Comparative cellular analysis of motor cortex in human, marmoset and mouse

Author

McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Bakken, Trygve E., Jorstad, Nikolas L., Hu, Qiwen, Lake, Blue B., Tian, Wei, Kalmbach, Brian E., Crow, Megan, Hodge, Rebecca D., Krienen, Fenna M., Sorensen, Staci A., Eggermont, Jeroen, Yao, Zizhen, Aevermann, Brian D., Aldridge, Andrew I., Bartlett, Anna, Bertagnolli, Darren, Casper, Tamara, Castanon, Rosa G., Crichton, Kirsten, Daigle, Tanya L., Dalley, Rachel, Dee, Nick, Dembrow, Nikolai, Diep, Dinh, Ding, Song-Lin, Dong, Weixiu, Fang, Rongxin, Fischer, Stephan, Goldman, Melissa, Goldy, Jeff, Graybuck, Lucas T., Herb, Brian R., Hou, Xiaomeng, Kancherla, Jayaram, Kroll, Matthew, Lathia, Kanan, van Lew, Baldur, Li, Yang Eric, Liu, Christine S., Liu, Hanqing, Lucero, Jacinta D., Mahurkar, Anup, McMillen, Delissa, Miller, Jeremy A., Moussa, Marmar, Nery, Joseph R., Nicovich, Philip R., Niu, Sheng-Yong, Orvis, Joshua, Osteen, Julia K., Owen, Scott, Palmer, Carter R., Pham, Thanh, Plongthongkum, Nongluk, Poirion, Olivier, Reed, Nora M., Rimorin, Christine, Rivkin, Angeline, Romanow, William J., Sedeño-Cortés, Adriana E., Siletti, Kimberly, Somasundaram, Saroja, Sulc, Josef, Tieu, Michael, Torkelson, Amy, Tung, Herman, Wang, Xinxin, Xie, Fangming, Yanny, Anna Marie, Zhang, Renee, Ament, Seth A., Behrens, M. Margarita, Bravo, Hector Corrada, Chun, Jerold, Dobin, Alexander, Gillis, Jesse, Hertzano, Ronna, Hof, Patrick R., Höllt, Thomas, Horwitz, Gregory D., Keene, C. Dirk, Kharchenko, Peter V., Ko, Andrew L., Lelieveldt, Boudewijn P., Luo, Chongyuan, Mukamel, Eran A., Pinto-Duarte, António, Preissl, Sebastian, Regev, Aviv, Ren, Bing, Scheuermann, Richard H., Smith, Kimberly, Spain, William J., White, Owen R., Koch, Christof, Hawrylycz, Michael, Tasic, Bosiljka, Macosko, Evan Z., McCarroll, Steven A., Ting, Jonathan T., Zeng, Hongkui, Zhang, Kun, Feng, Guoping, Ecker, Joseph R., Linnarsson, Sten, Lein, Ed S., McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Bakken, Trygve E., Jorstad, Nikolas L., Hu, Qiwen, Lake, Blue B., Tian, Wei, Kalmbach, Brian E., Crow, Megan, Hodge, Rebecca D., Krienen, Fenna M., Sorensen, Staci A., Eggermont, Jeroen, Yao, Zizhen, Aevermann, Brian D., Aldridge, Andrew I., Bartlett, Anna, Bertagnolli, Darren, Casper, Tamara, Castanon, Rosa G., Crichton, Kirsten, Daigle, Tanya L., Dalley, Rachel, Dee, Nick, Dembrow, Nikolai, Diep, Dinh, Ding, Song-Lin, Dong, Weixiu, Fang, Rongxin, Fischer, Stephan, Goldman, Melissa, Goldy, Jeff, Graybuck, Lucas T., Herb, Brian R., Hou, Xiaomeng, Kancherla, Jayaram, Kroll, Matthew, Lathia, Kanan, van Lew, Baldur, Li, Yang Eric, Liu, Christine S., Liu, Hanqing, Lucero, Jacinta D., Mahurkar, Anup, McMillen, Delissa, Miller, Jeremy A., Moussa, Marmar, Nery, Joseph R., Nicovich, Philip R., Niu, Sheng-Yong, Orvis, Joshua, Osteen, Julia K., Owen, Scott, Palmer, Carter R., Pham, Thanh, Plongthongkum, Nongluk, Poirion, Olivier, Reed, Nora M., Rimorin, Christine, Rivkin, Angeline, Romanow, William J., Sedeño-Cortés, Adriana E., Siletti, Kimberly, Somasundaram, Saroja, Sulc, Josef, Tieu, Michael, Torkelson, Amy, Tung, Herman, Wang, Xinxin, Xie, Fangming, Yanny, Anna Marie, Zhang, Renee, Ament, Seth A., Behrens, M. Margarita, Bravo, Hector Corrada, Chun, Jerold, Dobin, Alexander, Gillis, Jesse, Hertzano, Ronna, Hof, Patrick R., Höllt, Thomas, Horwitz, Gregory D., Keene, C. Dirk, Kharchenko, Peter V., Ko, Andrew L., Lelieveldt, Boudewijn P., Luo, Chongyuan, Mukamel, Eran A., Pinto-Duarte, António, Preissl, Sebastian, Regev, Aviv, Ren, Bing, Scheuermann, Richard H., Smith, Kimberly, Spain, William J., White, Owen R., Koch, Christof, Hawrylycz, Michael, Tasic, Bosiljka, Macosko, Evan Z., McCarroll, Steven A., Ting, Jonathan T., Zeng, Hongkui, Zhang, Kun, Feng, Guoping, Ecker, Joseph R., Linnarsson, Sten, and Lein, Ed S.

Abstract

AbstractThe primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals1. Here, using high-throughput transcriptomic and epigenomic profiling of more than 450,000 single nuclei in humans, marmoset monkeys and mice, we demonstrate a broadly conserved cellular makeup of this region, with similarities that mirror evolutionary distance and are consistent between the transcriptome and epigenome. The core conserved molecular identities of neuronal and non-neuronal cell types allow us to generate a cross-species consensus classification of cell types, and to infer conserved properties of cell types across species. Despite the overall conservation, however, many species-dependent specializations are apparent, including differences in cell-type proportions, gene expression, DNA methylation and chromatin state. Few cell-type marker genes are conserved across species, revealing a short list of candidate genes and regulatory mechanisms that are responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allows us to use patch–seq (a combination of whole-cell patch-clamp recordings, RNA sequencing and morphological characterization) to identify corticospinal Betz cells from layer 5 in non-human primates and humans, and to characterize their highly specialized physiology and anatomy. These findings highlight the robust molecular underpinnings of cell-type diversity in M1 across mammals, and point to the genes and regulatory pathways responsible for the functional identity of cell types and their species-specific adaptations.

Published
2022

47. Production of high fluence laser beams using ion wave plasma optics

Author

Kirkwood, R. K., primary, Poole, P. L., additional, Kalantar, D. H., additional, Chapman, T. D., additional, Wilks, S. C., additional, Edwards, M. R., additional, Turnbull, D. P., additional, Michel, P., additional, Divol, L., additional, Fisch, N. J., additional, Norreys, P., additional, Rozmus, W., additional, Bude, J., additional, Blue, B. E., additional, Fournier, K. B., additional, Van Wonterghem, B. M., additional, and MacKinnon, A., additional

Published
2022
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48. Lawson Criterion for Ignition Exceeded in an Inertial Fusion Experiment

Author

Abu-Shawareb, H, Acree, R, Adams, P, Adams, J, Addis, B, Aden, R, Adrian, P, Afeyan, BB, Aggleton, M, Aghaian, L, Aguirre, A, Aikens, D, Akre, J, Albert, F, Albrecht, M, Albright, BJ, Albritton, J, Alcala, J, Alday, C, Alessi, DA, Alexander, N, Alfonso, J, Alfonso, N, Alger, E, Ali, SJ, Ali, ZA, Alley, WE, Amala, P, Amendt, PA, Amick, P, Ammula, S, Amorin, C, Ampleford, DJ, Anderson, RW, Anklam, T, Antipa, N, Appelbe, B, Aracne-Ruddle, C, Araya, E, Arend, M, Arnold, P, Arnold, T, Asay, J, Atherton, LJ, Atkinson, D, Atkinson, R, Auerbach, JM, Austin, B, Auyang, L, Awwal, AS, Ayers, J, Ayers, S, Ayers, T, Azevedo, S, Bachmann, B, Back, CA, Bae, J, Bailey, DS, Bailey, J, Baisden, T, Baker, KL, Baldis, H, Barber, D, Barberis, M, Barker, D, Barnes, A, Barnes, CW, Barrios, MA, Barty, C, Bass, I, Batha, SH, Baxamusa, SH, Bazan, G, Beagle, JK, Beale, R, Beck, BR, Beck, JB, Bedzyk, M, Beeler, RG, Behrendt, W, Belk, L, Bell, P, Belyaev, M, Benage, JF, Bennett, G, Benedetti, LR, Benedict, LX, Berger, R, Bernat, T, Bernstein, LA, Berry, B, Bertolini, L, Besenbruch, G, Betcher, J, Bettenhausen, R, Betti, R, Bezzerides, B, Bhandarkar, SD, Bickel, R, Biener, J, Biesiada, T, Bigelow, K, Bigelow-Granillo, J, Bigman, V, Bionta, RM, Birge, NW, Bitter, M, Black, AC, Bleile, R, Bleuel, DL, Bliss, E, Blue, B, Boehly, T, Boehm, K, Boley, CD, Bonanno, R, Bond, EJ, Bond, T, Bonino, MJ, Borden, M, Bourgade, J-L, Bousquet, J, Bowers, J, Bowers, M, Boyd, R, Bozek, A, Bradley, DK, Bradley, KS, Bradley, PA, Bradley, L, Brannon, L, Brantley, PS, Braun, D, Braun, T, Brienza-Larsen, K, Briggs, TM, Britten, J, Brooks, ED, Browning, D, Bruhn, MW, Brunner, TA, Bruns, H, Brunton, G, Bryant, B, Buczek, T, Bude, J, Buitano, L, Burkhart, S, Burmark, J, Burnham, A, Burr, R, Busby, LE, Butlin, B, Cabeltis, R, Cable, M, Cabot, WH, Cagadas, B, Caggiano, J, Cahayag, R, Caldwell, SE, Calkins, S, Callahan, DA, Calleja-Aguirre, J, Camara, L, Camp, D, Campbell, EM, Campbell, JH, Carey, B, Carey, R, Carlisle, K, Carlson, L, Carman, L, Carmichael, J, Carpenter, A, Carr, C, Carrera, JA, Casavant, D, Casey, A, Casey, DT, Castillo, A, Castillo, E, Castor, JI, Castro, C, Caughey, W, Cavitt, R, Celeste, J, Celliers, PM, Cerjan, C, Chandler, G, Chang, B, Chang, C, Chang, J, Chang, L, Chapman, R, Chapman, T, Chase, L, Chen, H, Chen, K, Chen, L-Y, Cheng, B, Chittenden, J, Choate, C, Chou, J, Chrien, RE, Chrisp, M, Christensen, K, Christensen, M, Christopherson, AR, Chung, M, Church, JA, Clark, A, Clark, DS, Clark, K, Clark, R, Claus, L, Cline, B, Cline, JA, Cobble, JA, Cochrane, K, Cohen, B, Cohen, S, Collette, MR, Collins, G, Collins, LA, Collins, TJB, Conder, A, Conrad, B, Conyers, M, Cook, AW, Cook, D, Cook, R, Cooley, JC, Cooper, G, Cope, T, Copeland, SR, Coppari, F, Cortez, J, Cox, J, Crandall, DH, Crane, J, Craxton, RS, Cray, M, Crilly, A, Crippen, JW, Cross, D, Cuneo, M, Cuotts, G, Czajka, CE, Czechowicz, D, Daly, T, Danforth, P, Darbee, R, Darlington, B, Datte, P, Dauffy, L, Davalos, G, 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Hilsabeck, T, Hinkel, DE, Ho, DD, Ho, VK, Hoffer, JK, Hoffman, NM, Hohenberger, M, Hohensee, M, Hoke, W, Holdener, D, Holdener, F, Holder, JP, Holko, B, Holunga, D, Holzrichter, JF, Honig, J, Hoover, D, Hopkins, D, Berzak Hopkins, L, Hoppe, M, Hoppe, ML, Horner, J, Hornung, R, Horsfield, CJ, Horvath, J, Hotaling, D, House, R, Howell, L, Hsing, WW, Hu, SX, Huang, H, Huckins, J, Hui, H, Humbird, KD, Hund, J, Hunt, J, Hurricane, OA, Hutton, M, Huynh, KH-K, Inandan, L, Iglesias, C, Igumenshchev, IV, Izumi, N, Jackson, M, Jackson, J, Jacobs, SD, James, G, Jancaitis, K, Jarboe, J, Jarrott, LC, Jasion, D, Jaquez, J, Jeet, J, Jenei, AE, Jensen, J, Jimenez, J, Jimenez, R, Jobe, D, Johal, Z, Johns, HM, Johnson, D, Johnson, MA, Gatu Johnson, M, Johnson, RJ, Johnson, S, Johnson, SA, Johnson, T, Jones, K, Jones, O, Jones, M, Jorge, R, Jorgenson, HJ, Julian, M, Jun, BI, Jungquist, R, Kaae, J, Kabadi, N, Kaczala, D, Kalantar, D, Kangas, K, Karasiev, VV, Karasik, M, Karpenko, V, Kasarky, A, Kasper, K, Kauffman, R, Kaufman, MI, Keane, C, Keaty, L, Kegelmeyer, L, Keiter, PA, Kellett, PA, Kellogg, J, Kelly, JH, Kemic, S, Kemp, AJ, Kemp, GE, Kerbel, GD, Kershaw, D, Kerr, SM, Kessler, TJ, Key, MH, Khan, SF, Khater, H, Kiikka, C, Kilkenny, J, Kim, Y, Kim, Y-J, Kimko, J, Kimmel, M, Kindel, JM, King, J, Kirkwood, RK, Klaus, L, Klem, D, Kline, JL, Klingmann, J, Kluth, G, Knapp, P, Knauer, J, Knipping, J, Knudson, M, Kobs, D, Koch, J, Kohut, T, Kong, C, Koning, JM, Koning, P, Konior, S, Kornblum, H, Kot, LB, Kozioziemski, B, Kozlowski, M, Kozlowski, PM, Krammen, J, Krasheninnikova, NS, Kraus, B, Krauser, W, Kress, JD, Kritcher, AL, Krieger, E, Kroll, JJ, Kruer, WL, Kruse, MKG, Kucheyev, S, Kumbera, M, Kumpan, S, Kunimune, J, Kustowski, B, Kwan, TJT, Kyrala, GA, Laffite, S, Lafon, M, LaFortune, K, Lahmann, B, Lairson, B, Landen, OL, Langenbrunner, J, Lagin, L, Land, T, Lane, M, Laney, D, Langdon, AB, Langer, SH, Langro, A, Lanier, NE, Lanier, TE, Larson, D, Lasinski, BF, Lassle, D, LaTray, D, Lau, G, Lau, N, Laumann, C, Laurence, A, Laurence, TA, Lawson, J, Le, HP, Leach, RR, Leal, L, Leatherland, A, LeChien, K, Lechleiter, B, Lee, A, Lee, M, Lee, T, Leeper, RJ, Lefebvre, E, Leidinger, J-P, LeMire, B, Lemke, RW, Lemos, NC, Le Pape, S, Lerche, R, Lerner, S, Letts, S, Levedahl, K, Lewis, T, Li, CK, Li, H, Li, J, Liao, W, Liao, ZM, Liedahl, D, Liebman, J, Lindford, G, Lindman, EL, Lindl, JD, Loey, H, London, RA, Long, F, Loomis, EN, Lopez, FE, Lopez, H, Losbanos, E, Loucks, S, Lowe-Webb, R, Lundgren, E, Ludwigsen, AP, Luo, R, Lusk, J, Lyons, R, Ma, T, Macallop, Y, MacDonald, MJ, MacGowan, BJ, Mack, JM, Mackinnon, AJ, MacLaren, SA, MacPhee, AG, Magelssen, GR, Magoon, J, Malone, RM, Malsbury, T, Managan, R, Mancini, R, Manes, K, Maney, D, Manha, D, Mannion, OM, Manuel, AM, Mapoles, E, Mara, G, Marcotte, T, Marin, E, Marinak, MM, Mariscal, C, Mariscal, DA, Mariscal, EF, Marley, EV, Marozas, JA, Marquez, R, Marshall, CD, Marshall, FJ, Marshall, M, Marshall, S, Marticorena, J, Martinez, D, Maslennikov, I, Mason, D, Mason, RJ, Masse, L, Massey, W, Masson-Laborde, P-E, Masters, ND, Mathisen, D, Mathison, E, Matone, J, Matthews, MJ, Mattoon, C, Mattsson, TR, Matzen, K, Mauche, CW, Mauldin, M, McAbee, T, McBurney, M, Mccarville, T, McCrory, RL, McEvoy, AM, McGuffey, C, Mcinnis, M, McKenty, P, McKinley, MS, McLeod, JB, McPherson, A, Mcquillan, B, Meamber, M, Meaney, KD, Meezan, NB, Meissner, R, Mehlhorn, TA, Mehta, NC, Menapace, J, Merrill, FE, Merritt, BT, Merritt, EC, Meyerhofer, DD, Mezyk, S, Mich, RJ, Michel, PA, Milam, D, Miller, C, Miller, D, Miller, DS, Miller, E, Miller, EK, Miller, J, Miller, M, Miller, PE, Miller, T, Miller, W, Miller-Kamm, V, Millot, M, Milovich, JL, Minner, P, Miquel, J-L, Mitchell, S, Molvig, K, Montesanti, RC, Montgomery, DS, Monticelli, M, Montoya, A, Moody, JD, Moore, AS, Moore, E, Moran, M, Moreno, JC, Moreno, K, Morgan, BE, Morrow, T, Morton, JW, Moses, E, Moy, K, Muir, R, Murillo, MS, Murray, JE, Murray, JR, Munro, DH, Murphy, TJ, Munteanu, FM, Nafziger, J, Nagayama, T, Nagel, SR, Nast, R, Negres, RA, Nelson, A, Nelson, D, Nelson, J, Nelson, S, Nemethy, S, Neumayer, P, Newman, K, Newton, M, Nguyen, H, Di Nicola, J-MG, Di Nicola, P, Niemann, C, Nikroo, A, Nilson, PM, Nobile, A, Noorai, V, Nora, R, Norton, M, Nostrand, M, Note, V, Novell, S, Nowak, PF, Nunez, A, Nyholm, RA, O'Brien, M, Oceguera, A, Oertel, JA, Okui, J, Olejniczak, B, Oliveira, J, Olsen, P, Olson, B, Olson, K, Olson, RE, Opachich, YP, Orsi, N, Orth, CD, Owen, M, Padalino, S, Padilla, E, Paguio, R, Paguio, S, Paisner, J, Pajoom, S, Pak, A, Palaniyappan, S, Palma, K, Pannell, T, Papp, F, Paras, D, Parham, T, Park, H-S, Pasternak, A, Patankar, S, Patel, MV, Patel, PK, Patterson, R, Patterson, S, Paul, B, Paul, M, Pauli, E, Pearce, OT, Pearcy, J, Pedrotti, B, Peer, A, Pelz, LJ, Penetrante, B, Penner, J, Perez, A, Perkins, LJ, Pernice, E, Perry, TS, Person, S, Petersen, D, Petersen, T, Peterson, DL, Peterson, EB, Peterson, JE, Peterson, JL, Peterson, K, Peterson, RR, Petrasso, RD, Philippe, F, Phipps, TJ, Piceno, E, Ping, Y, Pickworth, L, Pino, J, Plummer, R, Pollack, GD, Pollaine, SM, Pollock, BB, Ponce, D, Ponce, J, Pontelandolfo, J, Porter, JL, Post, J, Poujade, O, Powell, C, Powell, H, Power, G, Pozulp, M, Prantil, M, Prasad, M, Pratuch, S, Price, S, Primdahl, K, Prisbrey, S, Procassini, R, Pruyne, A, Pudliner, B, Qiu, SR, Quan, K, Quinn, M, Quintenz, J, Radha, PB, Rainer, F, Ralph, JE, Raman, KS, Raman, R, Rambo, P, Rana, S, Randewich, A, Rardin, D, Ratledge, M, Ravelo, N, Ravizza, F, Rayce, M, Raymond, A, Raymond, B, Reed, B, Reed, C, Regan, S, Reichelt, B, Reis, V, Reisdorf, S, Rekow, V, Remington, BA, Rendon, A, Requieron, W, Rever, M, Reynolds, H, Reynolds, J, Rhodes, J, Rhodes, M, Richardson, MC, Rice, B, Rice, NG, Rieben, R, Rigatti, A, Riggs, S, Rinderknecht, HG, Ring, K, Riordan, B, Riquier, R, Rivers, C, Roberts, D, Roberts, V, Robertson, G, Robey, HF, Robles, J, Rocha, P, Rochau, G, Rodriguez, J, Rodriguez, S, Rosen, M, Rosenberg, M, Ross, G, Ross, JS, Ross, P, Rouse, J, Rovang, D, Rubenchik, AM, Rubery, MS, Ruiz, CL, Rushford, M, Russ, B, Rygg, JR, Ryujin, BS, Sacks, RA, Sacks, RF, Saito, K, Salmon, T, Salmonson, JD, Sanchez, J, Samuelson, S, Sanchez, M, Sangster, C, Saroyan, A, Sater, J, Satsangi, A, Sauers, S, Saunders, R, Sauppe, JP, Sawicki, R, Sayre, D, Scanlan, M, Schaffers, K, Schappert, GT, Schiaffino, S, Schlossberg, DJ, Schmidt, DW, Schmitt, MJ, Schneider, DHG, Schneider, MB, Schneider, R, Schoff, M, Schollmeier, M, Schölmerich, M, Schroeder, CR, Schrauth, SE, Scott, HA, Scott, I, Scott, JM, Scott, RHH, Scullard, CR, Sedillo, T, Seguin, FH, Seka, W, Senecal, J, Sepke, SM, Seppala, L, Sequoia, K, Severyn, J, Sevier, JM, Sewell, N, Seznec, S, Shah, RC, Shamlian, J, Shaughnessy, D, Shaw, M, Shaw, R, Shearer, C, Shelton, R, Shen, N, Sherlock, MW, Shestakov, AI, Shi, EL, Shin, SJ, Shingleton, N, Shmayda, W, Shor, M, Shoup, M, Shuldberg, C, Siegel, L, Silva, FJ, Simakov, AN, Sims, BT, Sinars, D, Singh, P, Sio, H, Skulina, K, Skupsky, S, Slutz, S, Sluyter, M, Smalyuk, VA, Smauley, D, Smeltser, RM, Smith, C, Smith, I, Smith, J, Smith, L, Smith, R, Sohn, R, Sommer, S, Sorce, C, Sorem, M, Soures, JM, Spaeth, ML, Spears, BK, Speas, S, Speck, D, Speck, R, Spears, J, Spinka, T, Springer, PT, Stadermann, M, Stahl, B, Stahoviak, J, Stanton, LG, Steele, R, Steele, W, Steinman, D, Stemke, R, Stephens, R, Sterbenz, S, Sterne, P, Stevens, D, Stevers, J, Still, CB, Stoeckl, C, Stoeffl, W, Stolken, JS, Stolz, C, Storm, E, Stone, G, Stoupin, S, Stout, E, Stowers, I, Strauser, R, Streckart, H, Streit, J, Strozzi, DJ, Suratwala, T, Sutcliffe, G, Suter, LJ, Sutton, SB, Svidzinski, V, Swadling, G, Sweet, W, Szoke, A, Tabak, M, Takagi, M, Tambazidis, A, Tang, V, Taranowski, M, Taylor, LA, Telford, S, Theobald, W, Thi, M, Thomas, A, Thomas, CA, Thomas, I, Thomas, R, Thompson, IJ, Thongstisubskul, A, Thorsness, CB, Tietbohl, G, Tipton, RE, Tobin, M, Tomlin, N, Tommasini, R, Toreja, AJ, Torres, J, Town, RPJ, Townsend, S, Trenholme, J, Trivelpiece, A, Trosseille, C, Truax, H, Trummer, D, Trummer, S, Truong, T, Tubbs, D, Tubman, ER, Tunnell, T, Turnbull, D, Turner, RE, Ulitsky, M, Upadhye, R, Vaher, JL, VanArsdall, P, VanBlarcom, D, Vandenboomgaerde, M, VanQuinlan, R, Van Wonterghem, BM, Varnum, WS, Velikovich, AL, Vella, A, Verdon, CP, Vermillion, B, Vernon, S, Vesey, R, Vickers, J, Vignes, RM, Visosky, M, Vocke, J, Volegov, PL, Vonhof, S, Von Rotz, R, Vu, HX, Vu, M, Wall, D, Wall, J, Wallace, R, Wallin, B, Walmer, D, Walsh, CA, Walters, CF, Waltz, C, Wan, A, Wang, A, Wang, Y, Wark, JS, Warner, BE, Watson, J, Watt, RG, Watts, P, Weaver, J, Weaver, RP, Weaver, S, Weber, CR, Weber, P, Weber, SV, Wegner, P, Welday, B, Welser-Sherrill, L, Weiss, K, Widmann, K, Wheeler, GF, Whistler, W, White, RK, Whitley, HD, Whitman, P, Wickett, ME, Widmayer, C, Wiedwald, J, Wilcox, R, Wilcox, S, Wild, C, Wilde, BH, Wilde, CH, Wilhelmsen, K, Wilke, MD, Wilkens, H, Wilkins, P, Wilks, SC, Williams, EA, Williams, GJ, Williams, W, Williams, WH, Wilson, DC, Wilson, B, Wilson, E, Wilson, R, Winters, S, Wisoff, J, Wittman, M, Wolfe, J, Wong, A, Wong, KW, Wong, L, Wong, N, Wood, R, Woodhouse, D, Woodruff, J, Woods, DT, Woods, S, Woodworth, BN, Wooten, E, Wootton, A, Work, K, Workman, JB, Wright, J, Wu, M, Wuest, C, Wysocki, FJ, Xu, H, Yamaguchi, M, Yang, B, Yang, ST, Yatabe, J, Yeamans, CB, Yee, BC, Yi, SA, Yin, L, Young, B, Young, CS, Young, CV, Young, P, Youngblood, K, Zacharias, R, Zagaris, G, Zaitseva, N, Zaka, F, Ze, F, Zeiger, B, Zika, M, Zimmerman, GB, Zobrist, T, Zuegel, JD, Zylstra, AB, Indirect Drive ICF Collaboration, Collaboration, Indirect Drive ICF, AWE Plc, Lawrence Livermore National Laboratory, and U.S Department of Energy

Subjects
General Physics, 02 Physical Sciences, General Physics and Astronomy, Indirect Drive ICF Collaboration, 01 Mathematical Sciences, 09 Engineering
Abstract

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

Published
2022

49. A Participant-Centered Approach to Understanding Risks and Benefits of Participation in Research Informed by the Kidney Precision Medicine Project

Author

Catherine R. Butler, Paul S. Appelbaum, Heather Ascani, Mark Aulisio, Catherine E. Campbell, Ian H. de Boer, Ashveena L. Dighe, Daniel E. Hall, Jonathan Himmelfarb, Richard Knight, Karla Mehl, Raghavan Murugan, Sylvia E. Rosas, John R. Sedor, John F. O’Toole, Katherine R. Tuttle, Sushrut S. Waikar, Michael Freeman, Theodore Alexandrov, Charles E. Alpers, Christopher R. Anderton, Joseph Ardayfio, Tanima Arora, Tarek M. El-Achkar, Evren U. Azeloglu, Olivia Balderes, Ulysses G.J. Balis, Shweta Bansal, Jonathan M. Barasch, Daria Barwinska, Jack Bebiak, Victoria M. Blanc, Kristina N. Blank, Andrew S. Bomback, Keith D. Brown, William S. Bush, Taneisha Campbell, Pietro A. Canetta, Jonas Carson, Leslie Cooperman, Dana C. Crawford, Vivette D. D’Agati, Pierre C. Dagher, Stephen Daniel, Frederick Dowd, Kenneth W. Dunn, Michael T. Eadon, Sean Eddy, Michele M. Elder, Michael J. Ferkowicz, Joe P. Gaut, Yury Goltsev, Agustin Gonzalez-Vicente, Nir Hacohen, Jens Hansen, Lynda Hayashi, Oliver He, Cijang He, S. Susan Hedayati, Leal Herlitz, Jeffrey B. Hodgin, Andrew N. Hoofnagle, Paul J. Hoover, Ravi Iyengar, Sanjay Jain, Nichole Jefferson, Stacey Jolly, John A. Kellum, Katherine J. Kelly, Asra Kermani, Krzysztof Kiryluk, Robert Koewler, Matthias Kretzler, Blue B. Lake, Zoltan G. Laszik, Stewart H. Lecker, Simon C. Lee, Chrysta Lienczewski, Christopher Y. Lu, Laura H. Mariani, Robyn L. McClelland, Gearoid M. McMahon, Steven Menez, Rajasree Menon, Tyler Miller, Orson W. Moe, Dennis Moledina, Sean D. Mooney, Jane Nguyen, Garry Nolan, George Oliver, Edgar Otto, Paul M. Palevsky, Ellen Palmer, Annapurna Pamreddy, Chirag R. Parikh, Samir Parikh, Christopher Park, Harold Park, Ljiljana Pasa-Tolic, Roy Pinkeney, Emilio Poggio, Parmjeet Randhawa, Helmut Rennke, Glenda V. Roberts, Avi Rosenberg, Matthew Rosengart, Brad Rovin, Neil Roy, Kamalanathan Sambandam, Minnie Sarwal, John Saul, Jennifer Schaub, Rachel Sealfon, Ning Shang, Stuart Shankland, Kumar Sharma, Anna Shpigel, Tara Sigdel, Becky Steck, Isaac Stillman, Edith Christine Stutzke, Timothy A. Sutton, Jose Torrealba, Robert D. Toto, Olga Troyanskaya, Mitchell Tublin, Ugochukwu Ugwuowo, Miguel Vazquez, Dusan Velickovic, Manjeri Venkatachalam, Anitha Vijayan, Celia P. Corona-Villalobos, Nancy Wang, Astrid Weins, Adam Wilcox, Kayleen Williams, Mark Williams, Francis P. Wilson, Seth Winfree, Yuguang Xiong, Kun Zhang, and Guanshi Zhang

Subjects
Informed Consent, Nephrology, Humans, Precision Medicine, Kidney, Risk Assessment, Article, Research Personnel
Abstract

An understanding of the ethical underpinnings of human subjects research that involves some risk to participants without anticipated direct clinical benefit-such as the kidney biopsy procedure as part of the Kidney Precision Medicine Project (KPMP)-requires a critical examination of the risks as well as the diverse set of countervailing potential benefits to participants. This kind of deliberation has been foundational to the development and conduct of the KPMP. Herein, we use illustrative features of this research paradigm to develop a more comprehensive conceptualization of the types of benefits that may be important to research participants, including respecting pluralistic values, supporting the opportunity to act altruistically, and enhancing benefits to a participant's community. This approach may serve as a model to help researchers, ethicists, and regulators to identify opportunities to better respect and support participants in future research that entails some risk to these participants as well as to improve the quality of research for people with kidney disease.

Published
2021

50. A multimodal cell census and atlas of the mammalian primary motor cortex

Author

Callaway, Edward M., Dong, Hong-Wei, Ecker, Joseph R., Hawrylycz, Michael J., Huang, Z. Josh, Lein, Ed S., Ngai, John, Osten, Pavel, Ren, Bing, Tolias, Andreas Savas, White, Owen, Zeng, Hongkui, Zhuang, Xiaowei, Ascoli, Giorgio A., Behrens, M. Margarita, Chun, Jerold, Feng, Guoping, Gee, James C., Ghosh, Satrajit S., Halchenko, Yaroslav O., Hertzano, Ronna, Lim, Byung Kook, Martone, Maryann E., Ng, Lydia, Pachter, Lior, Ropelewski, Alexander J., Tickle, Timothy L., Yang, X. William, Zhang, Kun, Bakken, Trygve E., Berens, Philipp, Daigle, Tanya L., Harris, Julie A., Jorstad, Nikolas L., Kalmbach, Brian E., Kobak, Dmitry, Li, Yang Eric, Liu, Hanqing, Matho, Katherine S., Mukamel, Eran A., Naeemi, Maitham, Scala, Federico, Tan, Pengcheng, Ting, Jonathan T., Xie, Fangming, Zhang, Meng, Zhang, Zhuzhu, Zhou, Jingtian, Zingg, Brian, Armand, Ethan, Yao, Zizhen, Bertagnolli, Darren, Casper, Tamara, Crichton, Kirsten, Dee, Nick, Diep, Dinh, Ding, Song-Lin, Dong, Weixiu, Dougherty, Elizabeth L., Fong, Olivia, Goldman, Melissa, Goldy, Jeff, Hodge, Rebecca D., Hu, Lijuan, Keene, C. Dirk, Krienen, Fenna M., Kroll, Matthew, Lake, Blue B., Lathia, Kanan, Linnarsson, Sten, Liu, Christine S., Macosko, Evan Z., McCarroll, Steven A., McMillen, Delissa, Nadaf, Naeem M., Nguyen, Thuc Nghi, Palmer, Carter R., Pham, Thanh, Plongthongkum, Nongluk, Reed, Nora M., Regev, Aviv, Rimorin, Christine, Romanow, William J., Savoia, Steven, Siletti, Kimberly, Smith, Kimberly, Sulc, Josef, Tasic, Bosiljka, Tieu, Michael, Torkelson, Amy, Tung, Herman, van Velthoven, Cindy T. J., Vanderburg, Charles R., Yanny, Anna Marie, Fang, Rongxin, Hou, Xiaomeng, Lucero, Jacinta D., Osteen, Julia K., Pinto-Duarte, Antonio, Poirion, Olivier, Preissl, Sebastian, Wang, Xinxin, Aldridge, Andrew I., Bartlett, Anna, Boggeman, Lara, O’Connor, Carolyn, Castanon, Rosa G., Chen, Huaming, Fitzpatrick, Conor, Luo, Chongyuan, Nery, Joseph R., Nunn, Michael, Rivkin, Angeline C., Tian, Wei, Dominguez, Bertha, Ito-Cole, Tony, Jacobs, Matthew, Jin, Xin, Lee, Cheng-Ta, Lee, Kuo-Fen, Miyazaki, Paula Assakura, Pang, Yan, Rashid, Mohammad, Smith, Jared B., Vu, Minh, Williams, Elora, Biancalani, Tommaso, Booeshaghi, A. Sina, Crow, Megan, Dudoit, Sandrine, Fischer, Stephan, Gillis, Jesse, Hu, Qiwen, Kharchenko, Peter V., Niu, Sheng-Yong, Ntranos, Vasilis, Purdom, Elizabeth, Risso, Davide, de Bézieux, Hector Roux, Somasundaram, Saroja, Street, Kelly, Svensson, Valentine, Vaishnav, Eeshit Dhaval, Van den Berge, Koen, Welch, Joshua D., An, Xu, Bateup, Helen S., Bowman, Ian, Chance, Rebecca K., Foster, Nicholas N., Galbavy, William, Gong, Hui, Gou, Lin, Hatfield, Joshua T., Hintiryan, Houri, Hirokawa, Karla E., Kim, Gukhan, Kramer, Daniel J., Li, Anan, Li, Xiangning, Luo, Qingming, Muñoz-Castañeda, Rodrigo, Stafford, David A., Feng, Zhao, Jia, Xueyan, Jiang, Shengdian, Jiang, Tao, Kuang, Xiuli, Larsen, Rachael, Lesnar, Phil, Li, Yaoyao, Li, Yuanyuan, Liu, Lijuan, Peng, Hanchuan, Qu, Lei, Ren, Miao, Ruan, Zongcai, Shen, Elise, Song, Yuanyuan, Wakeman, Wayne, Wang, Peng, Wang, Yimin, Wang, Yun, Yin, Lulu, Yuan, Jing, Zhao, Sujun, Zhao, Xuan, Narasimhan, Arun, Palaniswamy, Ramesh, Banerjee, Samik, Ding, Liya, Huilgol, Dhananjay, Huo, Bingxing, Kuo, Hsien-Chi, Laturnus, Sophie, Li, Xu, Mitra, Partha P., Mizrachi, Judith, Wang, Quanxin, Xie, Peng, Xiong, Feng, Yu, Yang, Eichhorn, Stephen W., Berg, Jim, Bernabucci, Matteo, Bernaerts, Yves, Cadwell, Cathryn René, Castro, Jesus Ramon, Dalley, Rachel, Hartmanis, Leonard, Horwitz, Gregory D., Jiang, Xiaolong, Ko, Andrew L., Miranda, Elanine, Mulherkar, Shalaka, Nicovich, Philip R., Owen, Scott F., Sandberg, Rickard, Sorensen, Staci A., Tan, Zheng Huan, Allen, Shona, Hockemeyer, Dirk, Lee, Angus Y., Veldman, Matthew B., Adkins, Ricky S., Ament, Seth A., Bravo, Héctor Corrada, Carter, Robert, Chatterjee, Apaala, Colantuoni, Carlo, Crabtree, Jonathan, Creasy, Heather, Felix, Victor, Giglio, Michelle, Herb, Brian R., Kancherla, Jayaram, Mahurkar, Anup, McCracken, Carrie, Nickel, Lance, Olley, Dustin, Orvis, Joshua, Schor, Michael, Hood, Greg, Dichter, Benjamin, Grauer, Michael, Helba, Brian, Bandrowski, Anita, Barkas, Nikolaos, Carlin, Benjamin, D’Orazi, Florence D., Degatano, Kylee, Gillespie, Thomas H., Khajouei, Farzaneh, Konwar, Kishori, Thompson, Carol, Kelly, Kathleen, Mok, Stephanie, Sunkin, Susan, BRAIN Initiative Cell Census Network (BICCN) Corresponding authors, [missing], BICCN contributing principal investigators, [missing], Principal manuscript editors, [missing], Manuscript writing and figure generation, [missing], Analysis coordination, [missing], Integrated data analysis, [missing], scRNA-seq and snRNA-seq data generation and processing, [missing], ATAC-seq data generation and processing, [missing], Methylcytosine data production and analysis, [missing], Epi-retro-seq data generation and processing, [missing], ‘Omics data analysis, [missing], Tracing and connectivity data generation, [missing], Morphology data generation and reconstruction, [missing], OLST/STPT and other data generation, [missing], Morphology, connectivity and imaging analysis, [missing], Spatially resolved single-cell transcriptomics (MERFISH), [missing], Multimodal profiling (Patch-seq), [missing], Transgenic tools, [missing], NeMO archive and analytics, [missing], Brain Image Library (BIL) archive, [missing], DANDI archive, [missing], Brain Cell Data Center (BCDC), [missing], Project management, [missing], and BRAIN Initiative Cell Census Network (BICCN), [missing]

Subjects
Epigenomics, Male, INTERNEURONS, ORGANIZATION, MOUSE, Molecular neuroscience, Neural circuits, CLASSIFICATION, Article, Mice, Atlases as Topic, Glutamates, Species Specificity, Animals, Humans, TRANSCRIPTOMICS, SPECIFICATION, NEURONS, In Situ Hybridization, Fluorescence, Phylogeny, Neurons, Multidisciplinary, Gene Expression Profiling, Biology and Life Sciences, PATHWAYS, Brain, Callithrix, Censuses, Cellular neuroscience, Mathematics and Statistics, SINGLE, Organ Specificity, MORPHOLOGY, Motor cortex, Female, Single-Cell Analysis, Transcriptome
Abstract

Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input–output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1–5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties., The BRAIN Initiative Cell Census Network has constructed a multimodal cell census and atlas of the mammalian primary motor cortex in a landmark effort towards understanding brain cell-type diversity, neural circuit organization and brain function.

Published
2021

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