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1. Expression of a mammalian RNA demethylase increases flower number and floral stem branching in Arabidopsis thaliana

Author

Markel, Kasey, Waldburger, Lucas, and Shih, Patrick M

Subjects
Plant Biology, Biological Sciences, Genetics, Plant biology
Abstract

Abstract: RNA methylation plays a central regulatory role in plant biology and is a relatively new target for plant improvement efforts. In nearly all cases, perturbation of the RNA methylation machinery results in deleterious phenotypes. However, a recent landmark paper reported that transcriptome‐wide use of the human RNA demethylase FTO substantially increased the yield of rice and potatoes. Here, we have performed the first independent replication of those results and demonstrated broader transferability of the trait, finding increased flower and fruit count in the model species Arabidopsis thaliana. We also performed RNA‐seq of our FTO‐transgenic plants, which we analyzed in conjunction with previously published datasets to detect several previously unrecognized patterns in the functional and structural classification of the upregulated and downregulated genes. From these, we present mechanistic hypotheses to explain these surprising results with the goal of spurring more widespread interest in this promising new approach to plant engineering.

Published
2024

2. Transcriptome architecture of the three main lineages of agrobacteria.

Author

Weisberg, Alexandra, Lee, Namil, Chang, Jeff, Shih, Patrick, Waldburger, Lucas, Keasling, Jay, and Thompson, Mitchell

Subjects
agrobacterium, comparative transcriptomics, differential RNA-seq, evolution, pathogenesis, transcription start sites, Transcriptome, Promoter Regions, Genetic, Genomics, Gene Expression Regulation, Nucleotides
Abstract

Agrobacteria are a diverse, polyphyletic group of prokaryotes with multipartite genomes capable of transferring DNA into the genomes of host plants, making them an essential tool in plant biotechnology. Despite their utility in plant transformation, genome-wide transcriptional regulation is not well understood across the three main lineages of agrobacteria. Transcription start sites (TSSs) are a necessary component of gene expression and regulation. In this study, we used differential RNA-seq and a TSS identification algorithm optimized on manually annotated TSS, then validated with existing TSS to identify thousands of TSS with nucleotide resolution for representatives of each lineage. We extend upon the 356 TSSs previously reported in Agrobacterium fabrum C58 by identifying 1,916 TSSs. In addition, we completed genomes and phenotyping of Rhizobium rhizogenes C16/80 and Allorhizobium vitis T60/94, identifying 2,650 and 2,432 TSSs, respectively. Parameter optimization was crucial for an accurate, high-resolution view of genome and transcriptional dynamics, highlighting the importance of algorithm optimization in genome-wide TSS identification and genomics at large. The optimized algorithm reduced the number of TSSs identified internal and antisense to the coding sequence on average by 90.5% and 91.9%, respectively. Comparison of TSS conservation between orthologs of the three lineages revealed differences in cell cycle regulation of ctrA as well as divergence of transcriptional regulation of chemotaxis-related genes when grown in conditions that simulate the plant environment. These results provide a framework to elucidate the mechanistic basis and evolution of pathology across the three main lineages of agrobacteria. IMPORTANCE Transcription start sites (TSSs) are fundamental for understanding gene expression and regulation. Agrobacteria, a group of prokaryotes with the ability to transfer DNA into the genomes of host plants, are widely used in plant biotechnology. However, the genome-wide transcriptional regulation of agrobacteria is not well understood, especially in less-studied lineages. Differential RNA-seq and an optimized algorithm enabled identification of thousands of TSSs with nucleotide resolution for representatives of each lineage. The results of this study provide a framework for elucidating the mechanistic basis and evolution of pathology across the three main lineages of agrobacteria. The optimized algorithm also highlights the importance of parameter optimization in genome-wide TSS identification and genomics at large.

Published
2023

3. The pGinger Family of Expression Plasmids

Author

Pearson, Allison N, Thompson, Mitchell G, Kirkpatrick, Liam D, Ho, Cindy, Vuu, Khanh M, Waldburger, Lucas M, Keasling, Jay D, and Shih, Patrick M

Subjects
Biochemistry and Cell Biology, Biological Sciences, Genetics, Biotechnology, Plasmids, Promoter Regions, Genetic, Escherichia coli, Metabolic Engineering, molecular genetics, plasmid, synthetic biology, Microbiology
Abstract

The pGinger suite of expression plasmids comprises 43 plasmids that will enable precise constitutive and inducible gene expression in a wide range of Gram-negative bacterial species. Constitutive vectors are composed of 16 synthetic constitutive promoters upstream of red fluorescent protein (RFP), with a broad-host-range BBR1 origin and a kanamycin resistance marker. The family also has seven inducible systems (Jungle Express, Psal/NahR, Pm/XylS, Prha/RhaS, LacO1/LacI, LacUV5/LacI, and Ptet/TetR) controlling RFP expression on BBR1/kanamycin plasmid backbones. For four of these inducible systems (Jungle Express, Psal/NahR, LacO1/LacI, and Ptet/TetR), we created variants that utilize the RK2 origin and spectinomycin or gentamicin selection. Relevant RFP expression and growth data have been collected in the model bacterium Escherichia coli as well as Pseudomonas putida. All pGinger vectors are available via the Joint BioEnergy Institute (JBEI) Public Registry. IMPORTANCE Metabolic engineering and synthetic biology are predicated on the precise control of gene expression. As synthetic biology expands beyond model organisms, more tools will be required that function robustly in a wide range of bacterial hosts. The pGinger family of plasmids constitutes 43 plasmids that will enable both constitutive and inducible gene expression in a wide range of nonmodel Proteobacteria.

Published
2023

4. Perspectives for self-driving labs in synthetic biology

Author

Martin, Hector Garcia, Radivojevic, Tijana, Zucker, Jeremy, Bouchard, Kristofer, Sustarich, Jess, Peisert, Sean, Arnold, Dan, Hillson, Nathan, Babnigg, Gyorgy, Marti, Jose Manuel, Mungall, Christopher J., Beckham, Gregg T., Waldburger, Lucas, Carothers, James, Sundaram, ShivShankar, Agarwal, Deb, Simmons, Blake A., Backman, Tyler, Banerjee, Deepanwita, Tanjore, Deepti, Ramakrishnan, Lavanya, and Singh, Anup

Subjects
Quantitative Biology - Other Quantitative Biology
Abstract

Self-driving labs (SDLs) combine fully automated experiments with artificial intelligence (AI) that decides the next set of experiments. Taken to their ultimate expression, SDLs could usher a new paradigm of scientific research, where the world is probed, interpreted, and explained by machines for human benefit. While there are functioning SDLs in the fields of chemistry and materials science, we contend that synthetic biology provides a unique opportunity since the genome provides a single target for affecting the incredibly wide repertoire of biological cell behavior. However, the level of investment required for the creation of biological SDLs is only warranted if directed towards solving difficult and enabling biological questions. Here, we discuss challenges and opportunities in creating SDLs for synthetic biology., Comment: 17 pages, 3 figures. Submitted for publication in Current Opinion in Biotechnology. Updated figure 3 in this version

Published
2022

5. Perspectives for self-driving labs in synthetic biology

Author

Martin, Hector G, Radivojevic, Tijana, Zucker, Jeremy, Bouchard, Kristofer, Sustarich, Jess, Peisert, Sean, Arnold, Dan, Hillson, Nathan, Babnigg, Gyorgy, Marti, Jose M, Mungall, Christopher J, Beckham, Gregg T, Waldburger, Lucas, Carothers, James, Sundaram, ShivShankar, Agarwal, Deb, Simmons, Blake A, Backman, Tyler, Banerjee, Deepanwita, Tanjore, Deepti, Ramakrishnan, Lavanya, and Singh, Anup

Subjects
Biochemistry and Cell Biology, Biological Sciences, Biotechnology, Human Genome, Genetics, Bioengineering, Humans, Artificial Intelligence, Synthetic Biology, q-bio.OT, Engineering, Technology, Agricultural biotechnology, Industrial biotechnology, Medical biotechnology
Abstract

Self-driving labs (SDLs) combine fully automated experiments with artificial intelligence (AI) that decides the next set of experiments. Taken to their ultimate expression, SDLs could usher a new paradigm of scientific research, where the world is probed, interpreted, and explained by machines for human benefit. While there are functioning SDLs in the fields of chemistry and materials science, we contend that synthetic biology provides a unique opportunity since the genome provides a single target for affecting the incredibly wide repertoire of biological cell behavior. However, the level of investment required for the creation of biological SDLs is only warranted if directed toward solving difficult and enabling biological questions. Here, we discuss challenges and opportunities in creating SDLs for synthetic biology.

Published
2023

6. Tandem repeats in giant archaeal Borg elements undergo rapid evolution and create new intrinsically disordered regions in proteins

Author

Schoelmerich, Marie Charlotte, Sachdeva, Rohan, West-Roberts, Jacob, Waldburger, Lucas, and Banfield, Jillian F

Subjects
Prevention, Archaea, Tandem Repeat Sequences, Proteins, Biological Sciences, Agricultural and Veterinary Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Borgs are huge, linear extrachromosomal elements associated with anaerobic methane-oxidizing archaea. Striking features of Borg genomes are pervasive tandem direct repeat (TR) regions. Here, we present six new Borg genomes and investigate the characteristics of TRs in all ten complete Borg genomes. We find that TR regions are rapidly evolving, recently formed, arise independently, and are virtually absent in host Methanoperedens genomes. Flanking partial repeats and A-enriched character constrain the TR formation mechanism. TRs can be in intergenic regions, where they might serve as regulatory RNAs, or in open reading frames (ORFs). TRs in ORFs are under very strong selective pressure, leading to perfect amino acid TRs (aaTRs) that are commonly intrinsically disordered regions. Proteins with aaTRs are often extracellular or membrane proteins, and functionally similar or homologous proteins often have aaTRs composed of the same amino acids. We propose that Borg aaTR-proteins functionally diversify Methanoperedens and all TRs are crucial for specific Borg-host associations and possibly cospeciation.

Published
2023

7. Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris

Author

Schaum, Nicholas, Karkanias, Jim, Neff, Norma F, May, Andrew P, Quake, Stephen R, Wyss-Coray, Tony, Darmanis, Spyros, Batson, Joshua, Botvinnik, Olga, Chen, Michelle B, Chen, Steven, Green, Foad, Jones, Robert C, Maynard, Ashley, Penland, Lolita, Pisco, Angela Oliveira, Sit, Rene V, Stanley, Geoffrey M, Webber, James T, Zanini, Fabio, Baghel, Ankit S, Bakerman, Isaac, Bansal, Ishita, Berdnik, Daniela, Bilen, Biter, Brownfield, Douglas, Cain, Corey, Cho, Min, Cirolia, Giana, Conley, Stephanie D, Demers, Aaron, Demir, Kubilay, de Morree, Antoine, Divita, Tessa, du Bois, Haley, Dulgeroff, Laughing Bear Torrez, Ebadi, Hamid, Espinoza, F Hernan, Fish, Matt, Gan, Qiang, George, Benson M, Gillich, Astrid, Genetiano, Geraldine, Gu, Xueying, Gulati, Gunsagar S, Hang, Yan, Hosseinzadeh, Shayan, Huang, Albin, Iram, Tal, Isobe, Taichi, Ives, Feather, Kao, Kevin S, Karnam, Guruswamy, Kershner, Aaron M, Kiss, Bernhard M, Kong, William, Kumar, Maya E, Lam, Jonathan Y, Lee, Davis P, Lee, Song E, Li, Guang, Li, Qingyun, Liu, Ling, Lo, Annie, Lu, Wan-Jin, Manjunath, Anoop, May, Kaia L, May, Oliver L, McKay, Marina, Metzger, Ross J, Mignardi, Marco, Min, Dullei, Nabhan, Ahmad N, Ng, Katharine M, Noh, Joseph, Patkar, Rasika, Peng, Weng Chuan, Puccinelli, Robert, Sikandar, Shaheen S, Sinha, Rahul, Szade, Krzysztof, Tan, Weilun, Tato, Cristina, Tellez, Krissie, Travaglini, Kyle J, Tropini, Carolina, Waldburger, Lucas, van Weele, Linda J, Wosczyna, Michael N, Xiang, Jinyi, Xue, Soso, Youngyunpipatkul, Justin, Zardeneta, Macy E, Zhang, Fan, Zhou, Lu, Castro, Paola, Croote, Derek, DeRisi, Joseph L, Kuo, Christin S, and Lehallier, Benoit

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, 1.5 Resources and infrastructure (underpinning), Generic health relevance, Animals, Cell Biology, Endothelial Cells, Female, Flow Cytometry, Gene Expression Profiling, Male, Mice, Mice, Inbred C57BL, Microfluidics, Organ Specificity, Single-Cell Analysis, T-Lymphocytes, Transcription Factors, Transcriptome, Tabula Muris Consortium, Overall coordination, Logistical coordination, Organ collection and processing, Library preparation and sequencing, Computational data analysis, Cell type annotation, Writing group, Supplemental text writing group, Principal investigators, General Science & Technology
Abstract

Here we present a compendium of single-cell transcriptomic data from the model organism Mus musculus that comprises more than 100,000 cells from 20 organs and tissues. These data represent a new resource for cell biology, reveal gene expression in poorly characterized cell populations and enable the direct and controlled comparison of gene expression in cell types that are shared between tissues, such as T lymphocytes and endothelial cells from different anatomical locations. Two distinct technical approaches were used for most organs: one approach, microfluidic droplet-based 3'-end counting, enabled the survey of thousands of cells at relatively low coverage, whereas the other, full-length transcript analysis based on fluorescence-activated cell sorting, enabled the characterization of cell types with high sensitivity and coverage. The cumulative data provide the foundation for an atlas of transcriptomic cell biology.

Published
2018

9. Genetically refactored Agrobacterium-mediated transformation

Author

Thompson, Mitchell, primary, Kirkpatrick, Liam D, additional, Geiselman, Gina M, additional, Waldburger, Lucas M, additional, Pearson, Allison N, additional, Szarzanowicz, Matthew, additional, Vuu, Khanh M, additional, Markel, Kasey, additional, Hummel, Nikkas FC, additional, Suazo, Dennis D, additional, Tahmin, Claudine, additional, Cui, Ruoming, additional, Liu, Shuying, additional, Cevallos, Jasmine, additional, Pannu, Hamreet, additional, Liu, Di, additional, Gin, Jennifer W, additional, Chen, Yan, additional, Petzold, Christopher J, additional, Gladden, John, additional, Keasling, Jay D, additional, Chang, Jeff H, additional, Weisberg, Alexandra J, additional, and Shih, Patrick M, additional

Published
2023
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12. Perspectives for self-driving labs in synthetic biology

Author

Martin, Hector G, primary, Radivojevic, Tijana, additional, Zucker, Jeremy, additional, Bouchard, Kristofer, additional, Sustarich, Jess, additional, Peisert, Sean, additional, Arnold, Dan, additional, Hillson, Nathan, additional, Babnigg, Gyorgy, additional, Marti, Jose M, additional, Mungall, Christopher J, additional, Beckham, Gregg T, additional, Waldburger, Lucas, additional, Carothers, James, additional, Sundaram, ShivShankar, additional, Agarwal, Deb, additional, Simmons, Blake A, additional, Backman, Tyler, additional, Banerjee, Deepanwita, additional, Tanjore, Deepti, additional, Ramakrishnan, Lavanya, additional, and Singh, Anup, additional

Published
2023
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13. The pGinger family of expression plasmids

Author

Pearson, Allison N., primary, Thompson, Mitchell G., additional, Kirkpatrick, Liam D., additional, Ho, Cindy, additional, Vuu, Khanh M., additional, Waldburger, Lucas M., additional, Keasling, Jay D., additional, and Shih, Patrick M., additional

Published
2023
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14. Molecular hallmarks of heterochronic parabiosis at single-cell resolution

Author

Pálovics, Róbert, Keller, Andreas, Schaum, Nicholas, Tan, Weilun, Fehlmann, Tobias, Borja, Michael, Kern, Fabian, Bonanno, Liana, Calcuttawala, Kruti, Webber, James, McGeever, Aaron, Almanzar, Nicole, Antony, Jane, Baghel, Ankit S., Bakerman, Isaac, Bansal, Ishita, Barres, Ben A., Beachy, Philip A., Berdnik, Daniela, Bilen, Biter, Brownfield, Douglas, Cain, Corey, Chan, Charles K. F., Chen, Michelle B., Clarke, Michael F., Conley, Stephanie D., Demers, Aaron, Demir, Kubilay, de Morree, Antoine, Divita, Tessa, du Bois, Haley, Ebadi, Hamid, Espinoza, F. Hernán, Fish, Matt, Gan, Qiang, George, Benson M., Gillich, Astrid, Gòmez-Sjöberg, Rafael, Green, Foad, Genetiano, Geraldine, Gu, Xueying, Gulati, Gunsagar S., Hahn, Oliver, Haney, Michael Seamus, Hang, Yan, Harris, Lincoln, He, Mu, Hosseinzadeh, Shayan, Huang, Albin, Huang, Kerwyn Casey, Iram, Tal, Isobe, Taichi, Ives, Feather, Jones, Robert C., Kao, Kevin S., Karnam, Guruswamy, Kershner, Aaron M., Khoury, Nathalie, Kim, Seung K., Kiss, Bernhard M., Kong, William, Krasnow, Mark A., Kumar, Maya E., Kuo, Christin S., Lam, Jonathan, Lee, Davis P., Lee, Song E., Lehallier, Benoit, Leventhal, Olivia, Li, Guang, Li, Qingyun, Liu, Ling, Lo, Annie, Lu, Wan-Jin, Lugo-Fagundo, Maria F., Manjunath, Anoop, May, Andrew P., Maynard, Ashley, McKay, Marina, McNerney, M. Windy, Merrill, Bryan, Metzger, Ross J., Mignardi, Marco, Min, Dullei, Nabhan, Ahmad N., Ng, Katharine M., Nguyen, Patricia K., Noh, Joseph, Nusse, Roel, Patkar, Rasika, Peng, Weng Chuan, Penland, Lolita, Pollard, Katherine, Puccinelli, Robert, Qi, Zhen, Rando, Thomas A., Rulifson, Eric J., Segal, Joe M., Sikandar, Shaheen S., Sinha, Rahul, Sit, Rene V., Sonnenburg, Justin, Staehli, Daniel, Szade, Krzysztof, Tan, Michelle, Tato, Cristina, Tellez, Krissie, Torrez Dulgeroff, Laughing Bear, Travaglini, Kyle J., Tropini, Carolina, Tsui, Margaret, Waldburger, Lucas, Wang, Bruce M., van Weele, Linda J., Weinberg, Kenneth, Weissman, Irving L., Wosczyna, Michael N., Wu, Sean M., Xiang, Jinyi, Xue, Soso, Yamauchi, Kevin A., Yang, Andrew C., Yerra, Lakshmi P., Youngyunpipatkul, Justin, Yu, Brian, Zanini, Fabio, Zardeneta, Macy E., Zee, Alexander, Zhao, Chunyu, Zhang, Fan, Zhang, Hui, Zhang, Martin Jinye, Zhou, Lu, Zou, James, Luo, Jian, Pisco, Angela Oliveira, Karkanias, Jim, Neff, Norma F., Darmanis, Spyros, Quake, Stephen R., and Wyss-Coray, Tony

Subjects
Aging, Multidisciplinary, Parabiosis, Mesenchymal Stem Cells, Hematopoietic Stem Cells, Article, Organ Specificity/genetics, Mitochondria, Electron Transport, Electron Transport/genetics, Organ Specificity, Aging/genetics, Adipocytes, Hepatocytes, Rejuvenation, RNA-Seq, Single-Cell Analysis
Abstract

The ability to slow or reverse biological ageing would have major implications for mitigating disease risk and maintaining vitality1. Although an increasing number of interventions show promise for rejuvenation2, their effectiveness on disparate cell types across the body and the molecular pathways susceptible to rejuvenation remain largely unexplored. Here we performed single-cell RNA sequencing on 20 organs to reveal cell-type-specific responses to young and aged blood in heterochronic parabiosis. Adipose mesenchymal stromal cells, haematopoietic stem cells and hepatocytes are among those cell types that are especially responsive. On the pathway level, young blood invokes new gene sets in addition to reversing established ageing patterns, with the global rescue of genes encoding electron transport chain subunits pinpointing a prominent role of mitochondrial function in parabiosis-mediated rejuvenation. We observed an almost universal loss of gene expression with age that is largely mimicked by parabiosis: aged blood reduces global gene expression, and young blood restores it in select cell types. Together, these data lay the groundwork for a systemic understanding of the interplay between blood-borne factors and cellular integrity.

Published
2022

17. Ageing hallmarks exhibit organ-specific temporal signatures

Author

Schaum, Nicholas, Lehallier, Benoit, Hahn, Oliver, Pálovics, Róbert, Hosseinzadeh, Shayan, Lee, Song E., Sit, Rene, Lee, Davis P., Losada, Patricia Morán, Zardeneta, Macy E., Fehlmann, Tobias, Webber, James T., McGeever, Aaron, Calcuttawala, Kruti, Zhang, Hui, Berdnik, Daniela, Mathur, Vidhu, Tan, Weilun, Zee, Alexander, Tan, Michelle, Almanzar, Nicole, Antony, Jane, Baghel, Ankit S., Bakerman, Isaac, Bansal, Ishita, Barres, Ben A., Beachy, Philip A., Bilen, Biter, Brownfield, Douglas, Cain, Corey, Chan, Charles K. F., Chen, Michelle B., Clarke, Michael F., Conley, Stephanie D., Darmanis, Spyros, Demers, Aaron, Demir, Kubilay, de Morree, Antoine, Divita, Tessa, du Bois, Haley, Ebadi, Hamid, Espinoza, F. Hernán, Fish, Matt, Gan, Qiang, George, Benson M., Gillich, Astrid, Gòmez-Sjöberg, Rafael, Green, Foad, Genetiano, Geraldine, Gu, Xueying, Gulati, Gunsagar S., Haney, Michael Seamus, Hang, Yan, Harris, Lincoln, He, Mu, Huang, Albin, Huang, Kerwyn Casey, Iram, Tal, Isobe, Taichi, Ives, Feather, Jones, Robert, Kao, Kevin S., Karkanias, Jim, Karnam, Guruswamy, Keller, Andreas, Kershner, Aaron M., Khoury, Nathalie, Kim, Seung K., Kiss, Bernhard M., Kong, William, Krasnow, Mark A., Kumar, Maya E., Kuo, Christin S., Lam, Jonathan Y., Leventhal, Olivia, Li, Guang, Li, Qingyun, Liu, Ling, Lo, Annie, Lu, Wan-Jin, Lugo-Fagundo, Maria F., Manjunath, Anoop, May, Andrew P., Maynard, Ashley, McKay, Marina, McNerney, M. Windy, Merrill, Bryan, Metzger, Ross J., Mignardi, Marco, Min, Dullei, Nabhan, Ahmad N., Neff, Norma F., Ng, Katharine M., Nguyen, Patricia K., Noh, Joseph, Nusse, Roel, Patkar, Rasika, Peng, Weng Chuan, Penland, Lolita, Pisco, Angela Oliveira, Pollard, Katherine, Puccinelli, Robert, Qi, Zhen, Quake, Stephen R., Rando, Thomas A., Rulifson, Eric J., Segal, Joe M., Sikandar, Shaheen S., Sinha, Rahul, Sonnenburg, Justin, Staehli, Daniel, Szade, Krzysztof, Tato, Cristina, Tellez, Krissie, Torrez Dulgeroff, Laughing Bear, Travaglini, Kyle J., Tropini, Carolina, Tsui, Margaret, Waldburger, Lucas, Wang, Bruce M., van Weele, Linda J., Weinberg, Kenneth, Weissman, Irving L., Wosczyna, Michael N., Wu, Sean M., Wyss-Coray, Tony, Xiang, Jinyi, Xue, Soso, Yamauchi, Kevin A., Yang, Andrew C., Yerra, Lakshmi P., Youngyunpipatkul, Justin, Yu, Brian, Zanini, Fabio, Zhao, Chunyu, Zhang, Fan, Zhang, Martin Jinye, Zhou, Lu, and Zou, James

Subjects
0301 basic medicine, Male, Aging, Time Factors, T-Lymphocytes, Plasma Cells, RNA-Seq, Biology, Article, Transcriptome, 03 medical and health sciences, Mice, 0302 clinical medicine, Gene expression, Animals, RNA, Messenger, Gene, Regulation of gene expression, Multidisciplinary, Blood Proteins, Cell biology, 030104 developmental biology, Proteostasis, Gene Expression Regulation, Ageing, Organ Specificity, Immunoglobulin J-Chains, Unfolded protein binding, Female, Single-Cell Analysis, 030217 neurology & neurosurgery
Abstract

Ageing is the single greatest cause of disease and death worldwide, and understanding the associated processes could vastly improve quality of life. Although major categories of ageing damage have been identified—such as altered intercellular communication, loss of proteostasis and eroded mitochondrial function1—these deleterious processes interact with extraordinary complexity within and between organs, and a comprehensive, whole-organism analysis of ageing dynamics has been lacking. Here we performed bulk RNA sequencing of 17 organs and plasma proteomics at 10 ages across the lifespan of Mus musculus, and integrated these findings with data from the accompanying Tabula Muris Senis2—or ‘Mouse Ageing Cell Atlas’—which follows on from the original Tabula Muris3. We reveal linear and nonlinear shifts in gene expression during ageing, with the associated genes clustered in consistent trajectory groups with coherent biological functions—including extracellular matrix regulation, unfolded protein binding, mitochondrial function, and inflammatory and immune response. Notably, these gene sets show similar expression across tissues, differing only in the amplitude and the age of onset of expression. Widespread activation of immune cells is especially pronounced, and is first detectable in white adipose depots during middle age. Single-cell RNA sequencing confirms the accumulation of T cells and B cells in adipose tissue—including plasma cells that express immunoglobulin J—which also accrue concurrently across diverse organs. Finally, we show how gene expression shifts in distinct tissues are highly correlated with corresponding protein levels in plasma, thus potentially contributing to the ageing of the systemic circulation. Together, these data demonstrate a similar yet asynchronous inter- and intra-organ progression of ageing, providing a foundation from which to track systemic sources of declining health at old age. Bulk RNA sequencing of organs and plasma proteomics at different ages across the mouse lifespan is integrated with data from the Tabula Muris Senis, a transcriptomic atlas of ageing mouse tissues, to describe organ-specific changes in gene expression during ageing.

Published
2020

18. Traditional Group Work Songs

Author

Waldburger, Lucas C.

Subjects
Work songs, Music therapy, Ethnomusicology, behavioral disciplines and activities, human activities, humanities
Abstract

Pre-industrial work songs performed in groups are an area of ethnomusicological literature that has not been sufficiently examined by music therapists. This capstone sought to critically examine ethnomusicological reports of work songs and uncover underlying themes that hold significant within the music therapy sphere. A literature review of multicultural work songs was conducted and organized by themes relevant to music therapy techniques and interventions. These themes were synthesized with literature on group music making, physiological elements of rhythmicization, synchrony and rhythmic entrainment, and different approaches to music therapy. Results pointed to an overlap between work songs and music therapy techniques, suggesting that work songs can better inform disciplines such as community music therapy and neurologic music therapy. Recommendations are made for developing music therapy interventions, working with different client populations and in different treatment settings, and improving music therapy education and multicultural competence. Limitations in the music therapy field and the scope of the capstone are discussed and directions for future research are presented.

Published
2018
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19. Single-cell transcriptomic characterization of 20 organs and tissues from individual mice creates a Tabula Muris

Author

Schaum, Nicholas, primary, Karkanias, Jim, additional, Neff, Norma F, additional, May, Andrew P., additional, Quake, Stephen R., additional, Wyss-Coray, Tony, additional, Darmanis, Spyros, additional, Batson, Joshua, additional, Botvinnik, Olga, additional, Chen, Michelle B., additional, Chen, Steven, additional, Green, Foad, additional, Jones, Robert, additional, Maynard, Ashley, additional, Penland, Lolita, additional, Sit, Rene V., additional, Stanley, Geoffrey M., additional, Webber, James T., additional, Zanini, Fabio, additional, Baghel, Ankit S., additional, Bakerman, Isaac, additional, Bansal, Ishita, additional, Berdnik, Daniela, additional, Bilen, Biter, additional, Brownfield, Douglas, additional, Cain, Corey, additional, Cho, Min, additional, Cirolia, Giana, additional, Conley, Stephanie D., additional, Demers, Aaron, additional, Demir, Kubilay, additional, Morree, Antoine de, additional, Divita, Tessa, additional, Bois, Haley du, additional, Dulgeroff, Laughing Bear Torrez, additional, Ebadi, Hamid, additional, Espinoza, F. Hernan, additional, Fish, Matt, additional, Gan, Qiang, additional, George, Benson M., additional, Gillich, Astrid, additional, Genetiano, Geraldine, additional, Gu, Xueying, additional, Gulati, Gunsagar S., additional, Hang, Yan, additional, Hosseinzadeh, Shayan, additional, Huang, Albin, additional, Iram, Tal, additional, Isobe, Taichi, additional, Ives, Feather, additional, Kao, Kevin S., additional, Karnam, Guruswamy, additional, Kershner, Aaron M., additional, Kiss, Bernhard, additional, Kong, William, additional, Kumar, Maya E., additional, Lam, Jonathan, additional, Lee, Davis P., additional, Lee, Song E., additional, Li, Guang, additional, Li, Qingyun, additional, Liu, Ling, additional, Lo, Annie, additional, Lu, Wan-Jin, additional, Manjunath, Anoop, additional, May, Kaia L., additional, May, Oliver L., additional, McKay, Marina, additional, Metzger, Ross J., additional, Mignardi, Marco, additional, Min, Dullei, additional, Nabhan, Ahmad N., additional, Ng, Katharine M., additional, Noh, Joseph, additional, Patkar, Rasika, additional, Peng, Weng Chuan, additional, Puccinelli, Robert, additional, Rulifson, Eric J., additional, Schaum, Nicholas, additional, Sikandar, Shaheen S., additional, Sinha, Rahul, additional, Sit, Rene V, additional, Szade, Krzysztof, additional, Tan, Weilun, additional, Tato, Cristina, additional, Tellez, Krissie, additional, Travaglini, Kyle J., additional, Tropini, Carolina, additional, Waldburger, Lucas, additional, Weele, Linda J. van, additional, Wosczyna, Michael N., additional, Xiang, Jinyi, additional, Xue, Soso, additional, Youngyunpipatkul, Justin, additional, Zardeneta, Macy E., additional, Zhang, Fan, additional, Zhou, Lu, additional, Neff, Norma F., additional, Castro, Paola, additional, Croote, Derek, additional, DeRisi, Joseph L., additional, Pisco, Angela, additional, Kiss, Bernhard M., additional, Kuo, Christin S., additional, Lehallier, Benoit, additional, Nguyen, Patricia K., additional, Tan, Serena Y., additional, Wang, Bruce M., additional, Yousef, Hanadie, additional, Beachy, Philip A., additional, Chan, Charles K. F., additional, Huang, Kerwyn Casey, additional, Weinberg, Kenneth, additional, Wu, Sean, additional, Barres, Ben A., additional, Clarke, Michael F., additional, Kim, Seung K., additional, Krasnow, Mark A., additional, Neff, Norma, additional, Nusse, Roel, additional, Rando, Thomas A., additional, Sonnenburg, Justin, additional, Weissman, Irving L., additional, and Wu, Sean M., additional

Published
2017
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