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159 results on '"Subramanian, Ayshwarya"'

1. Neuropeptide signalling orchestrates T cell differentiation

Author

Hou, Yu, Sun, Linyu, LaFleur, Martin W., Huang, Linglin, Lambden, Conner, Thakore, Pratiksha I., Geiger-Schuller, Kathryn, Kimura, Kimitoshi, Yan, Longjun, Zang, Yue, Tang, Ruihan, Shi, Jingwen, Barilla, Rocky, Deng, Liwen, Subramanian, Ayshwarya, Wallrapp, Antonia, Choi, Hee Sun, Kye, Yoon-Chul, Ashenberg, Orr, Schiebinger, Geoffrey, Doench, John G., Chiu, Isaac M., Regev, Aviv, Sharpe, Arlene H., and Kuchroo, Vijay K.

Published
2024
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2. The contribution of historical processes to contemporary extinction risk in placental mammals

Author

Wilder, Aryn P, Supple, Megan A, Subramanian, Ayshwarya, Mudide, Anish, Swofford, Ross, Serres-Armero, Aitor, Steiner, Cynthia, Koepfli, Klaus-Peter, Genereux, Diane P, Karlsson, Elinor K, Lindblad-Toh, Kerstin, Marques-Bonet, Tomas, Munoz Fuentes, Violeta, Foley, Kathleen, Meyer, Wynn K, Ryder, Oliver A, Shapiro, Beth, Andrews, Gregory, Armstrong, Joel C, Bianchi, Matteo, Birren, Bruce W, Bredemeyer, Kevin R, Breit, Ana M, Christmas, Matthew J, Clawson, Hiram, Damas, Joana, Di Palma, Federica, Diekhans, Mark, Dong, Michael X, Eizirik, Eduardo, Fan, Kaili, Fanter, Cornelia, Foley, Nicole M, Forsberg-Nilsson, Karin, Garcia, Carlos J, Gatesy, John, Gazal, Steven, Goodman, Linda, Grimshaw, Jenna, Halsey, Michaela K, Harris, Andrew J, Hickey, Glenn, Hiller, Michael, Hindle, Allyson G, Hubley, Robert M, Hughes, Graham M, Johnson, Jeremy, Juan, David, Kaplow, Irene M, Keough, Kathleen C, Kirilenko, Bogdan, Korstian, Jennifer M, Kowalczyk, Amanda, Kozyrev, Sergey V, Lawler, Alyssa J, Lawless, Colleen, Lehmann, Thomas, Levesque, Danielle L, Lewin, Harris A, Li, Xue, Lind, Abigail, Mackay-Smith, Ava, Marinescu, Voichita D, Mason, Victor C, Meadows, Jennifer RS, Moore, Jill E, Moreira, Lucas R, Moreno-Santillan, Diana D, Morrill, Kathleen M, Muntané, Gerard, Murphy, William J, Navarro, Arcadi, Nweeia, Martin, Ortmann, Sylvia, Osmanski, Austin, Paten, Benedict, Paulat, Nicole S, Pfenning, Andreas R, Phan, BaDoi N, Pollard, Katherine S, Pratt, Henry E, Ray, David A, Reilly, Steven K, Rosen, Jeb R, Ruf, Irina, Ryan, Louise, Sabeti, Pardis C, Schäffer, Daniel E, Serres, Aitor, Smit, Arian FA, Springer, Mark, and Srinivasan, Chaitanya

Subjects
Biological Sciences, Evolutionary Biology, Genetics, Behavioral and Social Science, Human Genome, Basic Behavioral and Social Science, Life on Land, Animals, Female, Pregnancy, Eutheria, Extinction, Biological, Genetic Variation, Genome, Population Density, Risk, Zoonomia Consortium‡, General Science & Technology
Abstract

Species persistence can be influenced by the amount, type, and distribution of diversity across the genome, suggesting a potential relationship between historical demography and resilience. In this study, we surveyed genetic variation across single genomes of 240 mammals that compose the Zoonomia alignment to evaluate how historical effective population size (Ne) affects heterozygosity and deleterious genetic load and how these factors may contribute to extinction risk. We find that species with smaller historical Ne carry a proportionally larger burden of deleterious alleles owing to long-term accumulation and fixation of genetic load and have a higher risk of extinction. This suggests that historical demography can inform contemporary resilience. Models that included genomic data were predictive of species' conservation status, suggesting that, in the absence of adequate census or ecological data, genomic information may provide an initial risk assessment.

Published
2023

4. Protective role for kidney TREM2high macrophages in obesity- and diabetes-induced kidney injury

Author

Subramanian, Ayshwarya, Vernon, Katherine A., Zhou, Yiming, Marshall, Jamie L., Alimova, Maria, Arevalo, Carlos, Zhang, Fan, Slyper, Michal, Waldman, Julia, Montesinos, Monica S., Dionne, Danielle, Nguyen, Lan T., Cuoco, Michael S., Dubinsky, Dan, Purnell, Jason, Keller, Keith, Sturner, Samuel H., Grinkevich, Elizabeth, Ghoshal, Ayan, Kotek, Amanda, Trivioli, Giorgio, Richoz, Nathan, Humphrey, Mary B., Darby, Isabella G., Miller, Sarah J., Xu, Yingping, Weins, Astrid, Chloe-Villani, Alexandra, Chang, Steven L., Kretzler, Matthias, Rosenblatt-Rosen, Orit, Shaw, Jillian L., Zimmerman, Kurt A., Clatworthy, Menna R., Regev, Aviv, and Greka, Anna

Published
2024
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5. Identification of a protective microglial state mediated by miR-155 and interferon-γ signaling in a mouse model of Alzheimer’s disease

Author

Yin, Zhuoran, Herron, Shawn, Silveira, Sebastian, Kleemann, Kilian, Gauthier, Christian, Mallah, Dania, Cheng, Yiran, Margeta, Milica A., Pitts, Kristen M., Barry, Jen-Li, Subramanian, Ayshwarya, Shorey, Hannah, Brandao, Wesley, Durao, Ana, Delpech, Jean-Christophe, Madore, Charlotte, Jedrychowski, Mark, Ajay, Amrendra K., Murugaiyan, Gopal, Hersh, Samuel W., Ikezu, Seiko, Ikezu, Tsuneya, and Butovsky, Oleg

Published
2023
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6. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.

Author

Muus, Christoph, Luecken, Malte, Eraslan, Gökcen, Sikkema, Lisa, Waghray, Avinash, Heimberg, Graham, Kobayashi, Yoshihiko, Vaishnav, Eeshit, Subramanian, Ayshwarya, Smillie, Christopher, Jagadeesh, Karthik, Duong, Elizabeth, Fiskin, Evgenij, Torlai Triglia, Elena, Ansari, Meshal, Cai, Peiwen, Lin, Brian, Buchanan, Justin, Chen, Sijia, Shu, Jian, Haber, Adam, Chung, Hattie, Montoro, Daniel, Adams, Taylor, Aliee, Hananeh, Allon, Samuel, Andrusivova, Zaneta, Angelidis, Ilias, Ashenberg, Orr, Bassler, Kevin, Bécavin, Christophe, Benhar, Inbal, Bergenstråhle, Joseph, Bergenstråhle, Ludvig, Bolt, Liam, Braun, Emelie, Bui, Linh, Callori, Steven, Chaffin, Mark, Chichelnitskiy, Evgeny, Chiou, Joshua, Conlon, Thomas, Cuoco, Michael, Cuomo, Anna, Deprez, Marie, Duclos, Grant, Fine, Denise, Fischer, David, Ghazanfar, Shila, Gillich, Astrid, Giotti, Bruno, Gould, Joshua, Guo, Minzhe, Gutierrez, Austin, Habermann, Arun, Harvey, Tyler, He, Peng, Hou, Xiaomeng, Hu, Lijuan, Hu, Yan, Jaiswal, Alok, Ji, Lu, Jiang, Peiyong, Kapellos, Theodoros, Kuo, Christin, Larsson, Ludvig, Leney-Greene, Michael, Lim, Kyungtae, Litviňuková, Monika, Ludwig, Leif, Lukassen, Soeren, Luo, Wendy, Maatz, Henrike, Madissoon, Elo, Mamanova, Lira, Manakongtreecheep, Kasidet, Leroy, Sylvie, Mayr, Christoph, Mbano, Ian, McAdams, Alexi, Nabhan, Ahmad, Nyquist, Sarah, Penland, Lolita, Poirion, Olivier, Poli, Sergio, Qi, CanCan, Queen, Rachel, Reichart, Daniel, Rosas, Ivan, Schupp, Jonas, Shea, Conor, Shi, Xingyi, Sinha, Rahul, Sit, Rene, Slowikowski, Kamil, Slyper, Michal, Smith, Neal, Sountoulidis, Alex, Strunz, Maximilian, and Sullivan, Travis

Subjects
Adult, Aged, Aged, 80 and over, Alveolar Epithelial Cells, Angiotensin-Converting Enzyme 2, COVID-19, Cathepsin L, Datasets as Topic, Demography, Female, Gene Expression Profiling, Host-Pathogen Interactions, Humans, Lung, Male, Middle Aged, Organ Specificity, Respiratory System, SARS-CoV-2, Sequence Analysis, RNA, Serine Endopeptidases, Single-Cell Analysis, Virus Internalization
Abstract

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.

Published
2021

7. Discovery of bioactive microbial gene products in inflammatory bowel disease

Author

Zhang, Yancong, Bhosle, Amrisha, Bae, Sena, McIver, Lauren J., Pishchany, Gleb, Accorsi, Emma K., Thompson, Kelsey N., Arze, Cesar, Wang, Ya, Subramanian, Ayshwarya, Kearney, Sean M., Pawluk, April, Plichta, Damian R., Rahnavard, Ali, Shafquat, Afrah, Xavier, Ramnik J., Vlamakis, Hera, Garrett, Wendy S., Krueger, Andy, Huttenhower, Curtis, and Franzosa, Eric A.

Published
2022
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8. Mouse fetal growth restriction through parental and fetal immune gene variation and intercellular communications cascade

Author

Kaur, Gurman, Porter, Caroline B. M., Ashenberg, Orr, Lee, Jack, Riesenfeld, Samantha J., Hofree, Matan, Aggelakopoulou, Maria, Subramanian, Ayshwarya, Kuttikkatte, Subita Balaram, Attfield, Kathrine E., Desel, Christiane A. E., Davies, Jessica L., Evans, Hayley G., Avraham-Davidi, Inbal, Nguyen, Lan T., Dionne, Danielle A., Neumann, Anna E., Jensen, Lise Torp, Barber, Thomas R., Soilleux, Elizabeth, Carrington, Mary, McVean, Gil, Rozenblatt-Rosen, Orit, Regev, Aviv, and Fugger, Lars

Published
2022
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10. Deep learning and alignment of spatially resolved single-cell transcriptomes with Tangram

Author

Biancalani, Tommaso, Scalia, Gabriele, Buffoni, Lorenzo, Avasthi, Raghav, Lu, Ziqing, Sanger, Aman, Tokcan, Neriman, Vanderburg, Charles R., Segerstolpe, Åsa, Zhang, Meng, Avraham-Davidi, Inbal, Vickovic, Sanja, Nitzan, Mor, Ma, Sai, Subramanian, Ayshwarya, Lipinski, Michal, Buenrostro, Jason, Brown, Nik Bear, Fanelli, Duccio, Zhuang, Xiaowei, Macosko, Evan Z., and Regev, Aviv

Published
2021
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11. COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets

Author

Delorey, Toni M., Ziegler, Carly G. K., Heimberg, Graham, Normand, Rachelly, Yang, Yiming, Segerstolpe, Åsa, Abbondanza, Domenic, Fleming, Stephen J., Subramanian, Ayshwarya, Montoro, Daniel T., Jagadeesh, Karthik A., Dey, Kushal K., Sen, Pritha, Slyper, Michal, Pita-Juárez, Yered H., Phillips, Devan, Biermann, Jana, Bloom-Ackermann, Zohar, Barkas, Nikolaos, Ganna, Andrea, Gomez, James, Melms, Johannes C., Katsyv, Igor, Normandin, Erica, Naderi, Pourya, Popov, Yury V., Raju, Siddharth S., Niezen, Sebastian, Tsai, Linus T.-Y., Siddle, Katherine J., Sud, Malika, Tran, Victoria M., Vellarikkal, Shamsudheen K., Wang, Yiping, Amir-Zilberstein, Liat, Atri, Deepak S., Beechem, Joseph, Brook, Olga R., Chen, Jonathan, Divakar, Prajan, Dorceus, Phylicia, Engreitz, Jesse M., Essene, Adam, Fitzgerald, Donna M., Fropf, Robin, Gazal, Steven, Gould, Joshua, Grzyb, John, Harvey, Tyler, Hecht, Jonathan, Hether, Tyler, Jané-Valbuena, Judit, Leney-Greene, Michael, Ma, Hui, McCabe, Cristin, McLoughlin, Daniel E., Miller, Eric M., Muus, Christoph, Niemi, Mari, Padera, Robert, Pan, Liuliu, Pant, Deepti, Pe’er, Carmel, Pfiffner-Borges, Jenna, Pinto, Christopher J., Plaisted, Jacob, Reeves, Jason, Ross, Marty, Rudy, Melissa, Rueckert, Erroll H., Siciliano, Michelle, Sturm, Alexander, Todres, Ellen, Waghray, Avinash, Warren, Sarah, Zhang, Shuting, Zollinger, Daniel R., Cosimi, Lisa, Gupta, Rajat M., Hacohen, Nir, Hibshoosh, Hanina, Hide, Winston, Price, Alkes L., Rajagopal, Jayaraj, Tata, Purushothama Rao, Riedel, Stefan, Szabo, Gyongyi, Tickle, Timothy L., Ellinor, Patrick T., Hung, Deborah, Sabeti, Pardis C., Novak, Richard, Rogers, Robert, Ingber, Donald E., Jiang, Z. Gordon, Juric, Dejan, Babadi, Mehrtash, Farhi, Samouil L., Izar, Benjamin, Stone, James R., Vlachos, Ioannis S., Solomon, Isaac H., Ashenberg, Orr, Porter, Caroline B. M., Li, Bo, Shalek, Alex K., Villani, Alexandra-Chloé, Rozenblatt-Rosen, Orit, and Regev, Aviv

Published
2021
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12. Emergence of a High-Plasticity Cell State during Lung Cancer Evolution

Author

Marjanovic, Nemanja Despot, Hofree, Matan, Chan, Jason E., Canner, David, Wu, Katherine, Trakala, Marianna, Hartmann, Griffin G., Smith, Olivia C., Kim, Jonathan Y., Evans, Kelly Victoria, Hudson, Anna, Ashenberg, Orr, Porter, Caroline B.M., Bejnood, Alborz, Subramanian, Ayshwarya, Pitter, Kenneth, Yan, Yan, Delorey, Toni, Phillips, Devan R., Shah, Nisargbhai, Chaudhary, Ojasvi, Tsankov, Alexander, Hollmann, Travis, Rekhtman, Natasha, Massion, Pierre P., Poirier, John T., Mazutis, Linas, Li, Ruifang, Lee, Joo-Hyeon, Amon, Angelika, Rudin, Charles M., Jacks, Tyler, Regev, Aviv, and Tammela, Tuomas

Published
2020
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13. Author Correction: Community-wide hackathons to identify central themes in single-cell multi-omics

Author

Cao, Kim-Anh Lê, Abadi, Al J., Davis-Marcisak, Emily F., Hsu, Lauren, Arora, Arshi, Coullomb, Alexis, Deshpande, Atul, Feng, Yuzhou, Jeganathan, Pratheepa, Loth, Melanie, Meng, Chen, Mu, Wancen, Pancaldi, Vera, Sankaran, Kris, Righelli, Dario, Singh, Amrit, Sodicoff, Joshua S., Stein-O’Brien, Genevieve L., Subramanian, Ayshwarya, Welch, Joshua D., You, Yue, Argelaguet, Ricard, Carey, Vincent J., Dries, Ruben, Greene, Casey S., Holmes, Susan, Love, Michael I., Ritchie, Matthew E., Yuan, Guo-Cheng, Culhane, Aedin C., and Fertig, Elana

Published
2021
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14. Community-wide hackathons to identify central themes in single-cell multi-omics

Author

Lê Cao, Kim-Anh, Abadi, Al J., Davis-Marcisak, Emily F., Hsu, Lauren, Arora, Arshi, Coullomb, Alexis, Deshpande, Atul, Feng, Yuzhou, Jeganathan, Pratheepa, Loth, Melanie, Meng, Chen, Mu, Wancen, Pancaldi, Vera, Sankaran, Kris, Righelli, Dario, Singh, Amrit, Sodicoff, Joshua S., Stein-O’Brien, Genevieve L., Subramanian, Ayshwarya, Welch, Joshua D., You, Yue, Argelaguet, Ricard, Carey, Vincent J., Dries, Ruben, Greene, Casey S., Holmes, Susan, Love, Michael I., Ritchie, Matthew E., Yuan, Guo-Cheng, Culhane, Aedin C., and Fertig, Elana

Published
2021
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15. A Cellular Taxonomy of the Bone Marrow Stroma in Homeostasis and Leukemia

Author

Baryawno, Ninib, Przybylski, Dariusz, Kowalczyk, Monika S., Kfoury, Youmna, Severe, Nicolas, Gustafsson, Karin, Kokkaliaris, Konstantinos D., Mercier, Francois, Tabaka, Marcin, Hofree, Matan, Dionne, Danielle, Papazian, Ani, Lee, Dongjun, Ashenberg, Orr, Subramanian, Ayshwarya, Vaishnav, Eeshit Dhaval, Rozenblatt-Rosen, Orit, Regev, Aviv, and Scadden, David T.

Published
2019
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16. Deletion of miR‐155 in microglia enhances their response to neurodegeneration and mitigates cognitive impairment in a mouse model of Alzheimer’s disease

Author

Yin, Zhuoran, primary, Herron, Shawn, additional, Silveira, Sebastian, additional, Kleemann, Kilian, additional, Gauthier, Christian, additional, Mallah, Dania, additional, Cheng, Caterina, additional, Margeta, Milica, additional, Pitts, Kristen, additional, Barry, Jen‐Li, additional, Subramanian, Ayshwarya, additional, Shorey, Hannah, additional, Brandao, Wesley N, additional, Durao, Ana, additional, Delpech, Jean Christophe, additional, Madore, Charlotte, additional, Jedrychowski, Mark P, additional, Ajay, Amrendra K., additional, Gopal, Murugaiyan, additional, Hersh, Samuel Walter, additional, Ikezu, Seiko, additional, Ikezu, Tsuneya, additional, and Butovsky, Oleg, additional

Published
2023
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18. Stability of the human faecal microbiome in a cohort of adult men

Author

Mehta, Raaj S., Abu-Ali, Galeb S., Drew, David A., Lloyd-Price, Jason, Subramanian, Ayshwarya, Lochhead, Paul, Joshi, Amit D., Ivey, Kerry L., Khalili, Hamed, Brown, Gordon T., DuLong, Casey, Song, Mingyang, Nguyen, Long H., Mallick, Himel, Rimm, Eric B., Izard, Jacques, Huttenhower, Curtis, and Chan, Andrew T.

Published
2018
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23. The contribution of historical processes to contemporary extinction risk in placental mammals

Author

Wilder, Aryn P., Supple, Megan A., Subramanian, Ayshwarya, Mudide, Anish, Swofford, Ross, Serres-Armero, Aitor, Steiner, Cynthia, Koepfli, Klaus -Peter, Genereux, Diane P., Karlsson, Elinor K., Lindblad-Toh, Kerstin, Marques-Bonet, Tomas, Fuentes, Violeta Munoz, Foley, Kathleen, Meyer, Wynn K., Ryder, Oliver A., Shapiro, Beth, Wilder, Aryn P., Supple, Megan A., Subramanian, Ayshwarya, Mudide, Anish, Swofford, Ross, Serres-Armero, Aitor, Steiner, Cynthia, Koepfli, Klaus -Peter, Genereux, Diane P., Karlsson, Elinor K., Lindblad-Toh, Kerstin, Marques-Bonet, Tomas, Fuentes, Violeta Munoz, Foley, Kathleen, Meyer, Wynn K., Ryder, Oliver A., and Shapiro, Beth

Abstract

Species persistence can be influenced by the amount, type, and distribution of diversity across the genome, suggesting a potential relationship between historical demography and resilience. In this study, we surveyed genetic variation across single genomes of 240 mammals that compose the Zoonomia alignment to evaluate how historical effective population size (Ne) affects heterozygosity and deleterious genetic load and how these factors may contribute to extinction risk. We find that species with smaller historical Ne carry a proportionally larger burden of deleterious alleles owing to long-term accumulation and fixation of genetic load and have a higher risk of extinction. This suggests that historical demography can inform contemporary resilience. Models that included genomic data were predictive of species' conservation status, suggesting that, in the absence of adequate census or ecological data, genomic information may provide an initial risk assessment.

Published
2023
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24. Tim-3 adapter protein Bat3 acts as an endogenous regulator of tolerogenic dendritic cell function

Author

Massachusetts Institute of Technology. Department of Biology, Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research at MIT, Tang, Ruihan, Acharya, Nandini, Subramanian, Ayshwarya, Purohit, Vinee, Tabaka, Marcin, Hou, Yu, He, Danyang, Dixon, Karen O, Lambden, Connor, Xia, Junrong, Rozenblatt-Rosen, Orit, Sobel, Raymond A, Wang, Chao, Regev, Aviv, Anderson, Ana C, Kuchroo, Vijay K, Massachusetts Institute of Technology. Department of Biology, Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research at MIT, Tang, Ruihan, Acharya, Nandini, Subramanian, Ayshwarya, Purohit, Vinee, Tabaka, Marcin, Hou, Yu, He, Danyang, Dixon, Karen O, Lambden, Connor, Xia, Junrong, Rozenblatt-Rosen, Orit, Sobel, Raymond A, Wang, Chao, Regev, Aviv, Anderson, Ana C, and Kuchroo, Vijay K

Abstract

Dendritic cells (DCs) sense environmental cues and adopt either an immune-stimulatory or regulatory phenotype, thereby fine-tuning immune responses. Identifying endogenous regulators that determine DC function can thus inform the development of therapeutic strategies for modulating the immune response in different disease contexts. Tim-3 plays an important role in regulating immune responses by inhibiting the activation status and the T cell priming ability of DC in the setting of cancer. Bat3 is an adaptor protein that binds to the tail of Tim-3; therefore, we studied its role in regulating the functional status of DCs. In murine models of autoimmunity (experimental autoimmune encephalomyelitis) and cancer (MC38-OVA–implanted tumor), lack of Bat3 expression in DCs alters the T cell compartment—it decreases TH1, TH17 and cytotoxic effector cells, increases regulatory T cells, and exhausted CD8+tumor-infiltrating lymphocytes, resulting in the attenuation of autoimmunity and acceleration of tumor growth. We found that Bat3 expression levels were differentially regulated by activating versus inhibitory stimuli in DCs, indicating a role for Bat3 in the functional calibration of DC phenotypes. Mechanistically, loss of Bat3 in DCs led to hyperactive unfolded protein response and redirected acetyl–coenzyme A to increase cell intrinsic steroidogenesis. The enhanced steroidogenesis in Bat3-deficient DC suppressed T cell response in a paracrine manner. Our findings identified Bat3 as an endogenous regulator of DC function, which has implications for DC-based immunotherapies.

Published
2023

25. Biology-inspired data-driven quality control for scientific discovery in single-cell transcriptomics

Author

Massachusetts Institute of Technology. Department of Mathematics, Subramanian, Ayshwarya, Alperovich, Mikhail, Yang, Yiming, Li, Bo, Massachusetts Institute of Technology. Department of Mathematics, Subramanian, Ayshwarya, Alperovich, Mikhail, Yang, Yiming, and Li, Bo

Abstract

Background Quality control (QC) of cells, a critical first step in single-cell RNA sequencing data analysis, has largely relied on arbitrarily fixed data-agnostic thresholds applied to QC metrics such as gene complexity and fraction of reads mapping to mitochondrial genes. The few existing data-driven approaches perform QC at the level of samples or studies without accounting for biological variation. Results We first demonstrate that QC metrics vary with both tissue and cell types across technologies, study conditions, and species. We then propose data-driven QC (ddqc), an unsupervised adaptive QC framework to perform flexible and data-driven QC at the level of cell types while retaining critical biological insights and improved power for downstream analysis. ddqc applies an adaptive threshold based on the median absolute deviation on four QC metrics (gene and UMI complexity, fraction of reads mapping to mitochondrial and ribosomal genes). ddqc retains over a third more cells when compared to conventional data-agnostic QC filters. Finally, we show that ddqc recovers biologically meaningful trends in gradation of gene complexity among cell types that can help answer questions of biological interest such as which cell types express the least and most number of transcripts overall, and ribosomal transcripts specifically. Conclusions ddqc retains cell types such as metabolically active parenchymal cells and specialized cells such as neutrophils which are often lost by conventional QC. Taken together, our work proposes a revised paradigm to quality filtering best practices—iterative QC, providing a data-driven QC framework compatible with observed biological diversity.

Published
2023

26. Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function

Author

Massachusetts Institute of Technology. Department of Biology, Eraslan, Gökcen, Drokhlyansky, Eugene, Anand, Shankara, Fiskin, Evgenij, Subramanian, Ayshwarya, Slyper, Michal, Wang, Jiali, Van Wittenberghe, Nicholas, Rouhana, John M, Waldman, Julia, Ashenberg, Orr, Lek, Monkol, Dionne, Danielle, Win, Thet Su, Cuoco, Michael S, Kuksenko, Olena, Tsankov, Alexander M, Branton, Philip A, Marshall, Jamie L, Greka, Anna, Getz, Gad, Segrè, Ayellet V, Aguet, François, Rozenblatt-Rosen, Orit, Ardlie, Kristin G, Regev, Aviv, Massachusetts Institute of Technology. Department of Biology, Eraslan, Gökcen, Drokhlyansky, Eugene, Anand, Shankara, Fiskin, Evgenij, Subramanian, Ayshwarya, Slyper, Michal, Wang, Jiali, Van Wittenberghe, Nicholas, Rouhana, John M, Waldman, Julia, Ashenberg, Orr, Lek, Monkol, Dionne, Danielle, Win, Thet Su, Cuoco, Michael S, Kuksenko, Olena, Tsankov, Alexander M, Branton, Philip A, Marshall, Jamie L, Greka, Anna, Getz, Gad, Segrè, Ayellet V, Aguet, François, Rozenblatt-Rosen, Orit, Ardlie, Kristin G, and Regev, Aviv

Abstract

Understanding gene function and regulation in homeostasis and disease requires knowledge of the cellular and tissue contexts in which genes are expressed. Here, we applied four single-nucleus RNA sequencing methods to eight diverse, archived, frozen tissue types from 16 donors and 25 samples, generating a cross-tissue atlas of 209,126 nuclei profiles, which we integrated across tissues, donors, and laboratory methods with a conditional variational autoencoder. Using the resulting cross-tissue atlas, we highlight shared and tissue-specific features of tissue-resident cell populations; identify cell types that might contribute to neuromuscular, metabolic, and immune components of monogenic diseases and the biological processes involved in their pathology; and determine cell types and gene modules that might underlie disease mechanisms for complex traits analyzed by genome-wide association studies.

Published
2023

27. Deep learning and alignment of spatially resolved single-cell transcriptomes with Tangram

Author

Massachusetts Institute of Technology. Department of Biology, Biancalani, Tommaso, Scalia, Gabriele, Buffoni, Lorenzo, Avasthi, Raghav, Lu, Ziqing, Sanger, Aman, Tokcan, Neriman, Vanderburg, Charles R, Segerstolpe, Åsa, Zhang, Meng, Avraham-Davidi, Inbal, Vickovic, Sanja, Nitzan, Mor, Ma, Sai, Subramanian, Ayshwarya, Lipinski, Michal, Buenrostro, Jason, Brown, Nik Bear, Fanelli, Duccio, Zhuang, Xiaowei, Macosko, Evan Z, Regev, Aviv, Massachusetts Institute of Technology. Department of Biology, Biancalani, Tommaso, Scalia, Gabriele, Buffoni, Lorenzo, Avasthi, Raghav, Lu, Ziqing, Sanger, Aman, Tokcan, Neriman, Vanderburg, Charles R, Segerstolpe, Åsa, Zhang, Meng, Avraham-Davidi, Inbal, Vickovic, Sanja, Nitzan, Mor, Ma, Sai, Subramanian, Ayshwarya, Lipinski, Michal, Buenrostro, Jason, Brown, Nik Bear, Fanelli, Duccio, Zhuang, Xiaowei, Macosko, Evan Z, and Regev, Aviv

Abstract

AbstractCharting an organs’ biological atlas requires us to spatially resolve the entire single-cell transcriptome, and to relate such cellular features to the anatomical scale. Single-cell and single-nucleus RNA-seq (sc/snRNA-seq) can profile cells comprehensively, but lose spatial information. Spatial transcriptomics allows for spatial measurements, but at lower resolution and with limited sensitivity. Targeted in situ technologies solve both issues, but are limited in gene throughput. To overcome these limitations we present Tangram, a method that aligns sc/snRNA-seq data to various forms of spatial data collected from the same region, including MERFISH, STARmap, smFISH, Spatial Transcriptomics (Visium) and histological images. Tangram can map any type of sc/snRNA-seq data, including multimodal data such as those from SHARE-seq, which we used to reveal spatial patterns of chromatin accessibility. We demonstrate Tangram on healthy mouse brain tissue, by reconstructing a genome-wide anatomically integrated spatial map at single-cell resolution of the visual and somatomotor areas.

Published
2023

28. The contribution of historical processes to contemporary extinction risk in placental mammals

Author

National Institutes of Health (US), Swedish Research Council, European Research Council, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Howard Hughes Medical Institute, Generalitat de Catalunya, Marqués-Bonet, Tomàs [0000-0002-5597-3075], Juan, David [0000-0003-1912-9667], Muntané, Gerard [0000-0003-1541-8365], Navarro, Arcadi [0000-0003-2162-8246], Valenzuela, Alejandro [0000-0001-6120-6246], Wilder, Aryn P., Supple, Megan A., Subramanian, Ayshwarya, Mudide, Anish, Swofford, Ross, Serres-Armero, Aitor, Steiner, Cynthia, Koepfli, Klaus-Peter, Genereux, Diane P., Karlsson, Elinor K., Lindblad-Toh, Kerstin, Marqués-Bonet, Tomàs, Muñoz-Fuentes, Violeta, Foley, Kathleen, Meyer, Wynn K., Zoonomia Consortium, Juan, David, Muntané, Gerard, Navarro, Arcadi, Valenzuela, Alejandro, Ryder, Oliver A., Shapiro, Beth, National Institutes of Health (US), Swedish Research Council, European Research Council, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Howard Hughes Medical Institute, Generalitat de Catalunya, Marqués-Bonet, Tomàs [0000-0002-5597-3075], Juan, David [0000-0003-1912-9667], Muntané, Gerard [0000-0003-1541-8365], Navarro, Arcadi [0000-0003-2162-8246], Valenzuela, Alejandro [0000-0001-6120-6246], Wilder, Aryn P., Supple, Megan A., Subramanian, Ayshwarya, Mudide, Anish, Swofford, Ross, Serres-Armero, Aitor, Steiner, Cynthia, Koepfli, Klaus-Peter, Genereux, Diane P., Karlsson, Elinor K., Lindblad-Toh, Kerstin, Marqués-Bonet, Tomàs, Muñoz-Fuentes, Violeta, Foley, Kathleen, Meyer, Wynn K., Zoonomia Consortium, Juan, David, Muntané, Gerard, Navarro, Arcadi, Valenzuela, Alejandro, Ryder, Oliver A., and Shapiro, Beth

Abstract

[INTRODUCTION] The Anthropocene is marked by an accelerated loss of biodiversity, widespread population declines, and a global conservation crisis. Given limited resources for conservation intervention, an approach is needed to identify threatened species from among the thousands lacking adequate information for status assessments. Such prioritization for intervention could come from genome sequence data, as genomes contain information about demography, diversity, fitness, and adaptive potential. However, the relevance of genomic data for identifying at-risk species is uncertain, in part because genetic variation may reflect past events and life histories better than contemporary conservation status., [RATIONALE] The Zoonomia multispecies alignment presents an opportunity to systematically compare neutral and functional genomic diversity and their relationships to contemporary extinction risk across a large sample of diverse mammalian taxa. We surveyed 240 species spanning from the “Least Concern” to “Critically Endangered” categories, as published in the International Union for Conservation of Nature’s Red List of Threatened Species. Using a single genome for each species, we estimated historical effective population sizes (Ne) and distributions of genome-wide heterozygosity. To estimate genetic load, we identified substitutions relative to reconstructed ancestral sequences, assuming that mutations at evolutionarily conserved sites and in protein-coding sequences, especially in genes essential for viability in mice, are predominantly deleterious. We examined relationships between the conservation status of species and metrics of heterozygosity, demography, and genetic load and used these data to train and test models to distinguish threatened from nonthreatened species., [RESULTS] Species with smaller historical Ne are more likely to be categorized as at risk of extinction, suggesting that demography, even from periods more than 10,000 years in the past, may be informative of contemporary resilience. Species with smaller historical Ne also carry proportionally higher burdens of weakly and moderately deleterious alleles, consistent with theoretical expectations of the long-term accumulation and fixation of genetic load under strong genetic drift. We found weak support for a causative link between fixed drift load and extinction risk; however, other types of genetic load not captured in our data, such as rare, highly deleterious alleles, may also play a role. Although ecological (e.g., physiological, life-history, and behavioral) variables were the best predictors of extinction risk, genomic variables nonrandomly distinguished threatened from nonthreatened species in regression and machine learning models. These results suggest that information encoded within even a single genome can provide a risk assessment in the absence of adequate ecological or population census data., [CONCLUSION] Our analysis highlights the potential for genomic data to rapidly and inexpensively gauge extinction risk by leveraging relationships between contemporary conservation status and genetic variation shaped by the long-term demographic history of species. As more resequencing data and additional reference genomes become available, estimates of genetic load, estimates of recent demographic history, and accuracy of predictive models will improve. We therefore echo calls for including genomic information in assessments of the conservation status of species.

Published
2023

32. A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients

Author

Pita-Juarez, Yered, primary, Karagkouni, Dimitra, additional, Kalavros, Nikolaos, additional, Melms, Johannes C., additional, Niezen, Sebastian, additional, Delorey, Toni M., additional, Essene, Adam L, additional, Brook, Olga R., additional, Pant, Deepti, additional, Skelton-Badlani, Disha, additional, Naderi, Pourya, additional, Huang, Pinzhu, additional, Pan, Liuliu, additional, Hether, Tyler, additional, Andrews, Tallulah S., additional, Ziegler, Carly G.K., additional, Reeves, Jason, additional, Myloserdnyy, Andriy, additional, Chen, Rachel, additional, Nam, Andy, additional, Phelan, Stefan, additional, Liang, Yan, additional, Amin, Amit Dipak, additional, Biermann, Jana, additional, Hibshoosh, Hanina, additional, Veregge, Molly, additional, Kramer, Zachary, additional, Jacobs, Christopher, additional, Yalcin, Yusuf, additional, Phillips, Devan, additional, Slyper, Michal, additional, Subramanian, Ayshwarya, additional, Ashenberg, Orr, additional, Bloom-Ackermann, Zohar, additional, Tran, Victoria M., additional, Gomez, James, additional, Sturm, Alexander, additional, Zhang, Shuting, additional, Fleming, Stephen J., additional, Warren, Sarah, additional, Beechem, Joseph, additional, Hung, Deborah, additional, Babadi, Mehrtash, additional, Padera, Robert F., additional, MacParland, Sonya A., additional, Bader, Gary D., additional, Imad, Nasser, additional, Solomon, Isaac H., additional, Miller, Eric, additional, Riedel, Stefan, additional, Porter, Caroline B.M., additional, Villani, Alexandra-Chloé, additional, Tsai, Linus T.-Y., additional, Hide, Winston, additional, Szabo, Gyongyi, additional, Hecht, Jonathan, additional, Rozenblatt-Rosen, Orit, additional, Shalek, Alex K., additional, Izar, Benjamin, additional, Regev, Aviv, additional, Popov, Yury, additional, Jiang, Z. Gordon, additional, and Vlachos, Ioannis S., additional

Published
2022
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33. CRISPR screens reveal neuropeptide signaling orchestrates T helper cell differentiation

Author

Kuchroo, Vijay, primary, Hou, Yu, additional, LaFleur, Martin, additional, Huang, Linglin, additional, Lambden, Conner, additional, Thakore, Pratiksha, additional, Geiger-Schuller, Kathryn, additional, Tang, Ruihan, additional, Shi, Jingwen, additional, Barilla, Rocky, additional, Subramanian, Ayshwarya, additional, Wallrapp, Antonia, additional, Choi, Hee Sun, additional, Kye, Yoon-Chul, additional, Ashenbrg, Orr, additional, Schiebinger, Geoffrey, additional, Doench, John, additional, Regev, Aviv, additional, and Sharpe, Arlene, additional

Published
2022
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34. Gut CD4+ T cell phenotypes are a continuum molded by microbes, not by TH archetypes

Author

Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Kiner, Evgeny, Willie, Elijah, Vijaykumar, Brinda, Chowdhary, Kaitavjeet, Schmutz, Hugo, Chandler, Jodie, Schnell, Alexandra, Thakore, Pratiksha I., LeGros, Graham, Mostafavi, Sara, Mathis, Diane, Benoist, Christophe, Aguilar, Oscar, Allan, Rhys, Astarita, Jilian, Austen, K. Frank, Barrett, Nora, Baysoy, Alev, Brown, Brian D., Buechler, Matthew, Buenrostro, Jason, Casanova, Maria Acebes, Choi, Kyunghee, Colonna, Marco, Crowl, Ty, Deng, Tianda, Desai, Jigar V., Desland, Fiona, Dhainaut, Maxime, Ding, Jiarui, Dominguez, Claudia, Dwyer, Daniel, Frascoli, Michela, Gal-Oz, Shani, Goldrath, Ananda, Grieshaber-Bouyer, Ricardo, Jia, Baosen, Johanson, Tim, Jordan, Stefan, Kang, Joonsoo, Kapoor, Varun, Kenigsberg, Ephraim, Kim, Joel, wook Kim, Ki, Kronenberg, Mitchell, Lanier, Lewis, Laplace, Catherine, Lareau, Caleb, Leader, Andrew, Lee, Jisu, Magen, Assaf, Maier, Barbara, Maslova, Alexandra, McFarland, Adelle, Merad, Miriam, Meunier, Etienne, Monach, Paul, Muller, Soren, Muus, Christoph, Ner-Gaon, Hadas, Nguyen, Quyhn, Nigrovic, Peter A., Novakovsky, German, Nutt, Stephen, Omilusik, Kayla, Ortiz-Lopez, Adriana, Paynich, Mallory, Peng, Vincent, Potempa, Marc, Pradhan, Rachana, Quon, Sara, Ramirez, Ricardo, Ramanan, Deepshika, Randolph, Gwendalyn, Regev, Aviv, Rose, Samuel A., Seddu, Kumba, Shay, Tal, Shemesh, Avishai, Shyer, Justin, Smilie, Christopher, Spidale, Nick, Subramanian, Ayshwarya, Sylvia, Katelyn, Tellier, Julie, Turley, Shannon, Wagers, Amy, Wang, Chendi, Wang, Peter L., Wroblewska, Aleksandra, Yang, Liang, Yim, Aldrin, Yoshida, Hideyuki, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Kiner, Evgeny, Willie, Elijah, Vijaykumar, Brinda, Chowdhary, Kaitavjeet, Schmutz, Hugo, Chandler, Jodie, Schnell, Alexandra, Thakore, Pratiksha I., LeGros, Graham, Mostafavi, Sara, Mathis, Diane, Benoist, Christophe, Aguilar, Oscar, Allan, Rhys, Astarita, Jilian, Austen, K. Frank, Barrett, Nora, Baysoy, Alev, Brown, Brian D., Buechler, Matthew, Buenrostro, Jason, Casanova, Maria Acebes, Choi, Kyunghee, Colonna, Marco, Crowl, Ty, Deng, Tianda, Desai, Jigar V., Desland, Fiona, Dhainaut, Maxime, Ding, Jiarui, Dominguez, Claudia, Dwyer, Daniel, Frascoli, Michela, Gal-Oz, Shani, Goldrath, Ananda, Grieshaber-Bouyer, Ricardo, Jia, Baosen, Johanson, Tim, Jordan, Stefan, Kang, Joonsoo, Kapoor, Varun, Kenigsberg, Ephraim, Kim, Joel, wook Kim, Ki, Kronenberg, Mitchell, Lanier, Lewis, Laplace, Catherine, Lareau, Caleb, Leader, Andrew, Lee, Jisu, Magen, Assaf, Maier, Barbara, Maslova, Alexandra, McFarland, Adelle, Merad, Miriam, Meunier, Etienne, Monach, Paul, Muller, Soren, Muus, Christoph, Ner-Gaon, Hadas, Nguyen, Quyhn, Nigrovic, Peter A., Novakovsky, German, Nutt, Stephen, Omilusik, Kayla, Ortiz-Lopez, Adriana, Paynich, Mallory, Peng, Vincent, Potempa, Marc, Pradhan, Rachana, Quon, Sara, Ramirez, Ricardo, Ramanan, Deepshika, Randolph, Gwendalyn, Regev, Aviv, Rose, Samuel A., Seddu, Kumba, Shay, Tal, Shemesh, Avishai, Shyer, Justin, Smilie, Christopher, Spidale, Nick, Subramanian, Ayshwarya, Sylvia, Katelyn, Tellier, Julie, Turley, Shannon, Wagers, Amy, Wang, Chendi, Wang, Peter L., Wroblewska, Aleksandra, Yang, Liang, Yim, Aldrin, and Yoshida, Hideyuki

Published
2022

35. Emergence of a High-Plasticity Cell State during Lung Cancer Evolution

Author

Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Computational and Systems Biology Program, Massachusetts Institute of Technology. Department of Biology, Howard Hughes Medical Institute, Marjanovic, Nemanja Despot, Hofree, Matan, Chan, Jason E., Canner, David, Wu, Katherine, Trakala, Marianna, Hartmann, Griffin G., Smith, Olivia C., Kim, Jonathan Y., Evans, Kelly Victoria, Hudson, Anna, Ashenberg, Orr, Porter, Caroline B.M., Bejnood, Alborz, Subramanian, Ayshwarya, Pitter, Kenneth, Yan, Yan, Delorey, Toni, Phillips, Devan R., Shah, Nisargbhai, Chaudhary, Ojasvi, Tsankov, Alexander, Hollmann, Travis, Rekhtman, Natasha, Massion, Pierre P., Poirier, John T., Mazutis, Linas, Li, Ruifang, Lee, Joo-Hyeon, Amon, Angelika, Rudin, Charles M., Jacks, Tyler, Regev, Aviv, Tammela, Tuomas, Koch Institute for Integrative Cancer Research at MIT, Massachusetts Institute of Technology. Computational and Systems Biology Program, Massachusetts Institute of Technology. Department of Biology, Howard Hughes Medical Institute, Marjanovic, Nemanja Despot, Hofree, Matan, Chan, Jason E., Canner, David, Wu, Katherine, Trakala, Marianna, Hartmann, Griffin G., Smith, Olivia C., Kim, Jonathan Y., Evans, Kelly Victoria, Hudson, Anna, Ashenberg, Orr, Porter, Caroline B.M., Bejnood, Alborz, Subramanian, Ayshwarya, Pitter, Kenneth, Yan, Yan, Delorey, Toni, Phillips, Devan R., Shah, Nisargbhai, Chaudhary, Ojasvi, Tsankov, Alexander, Hollmann, Travis, Rekhtman, Natasha, Massion, Pierre P., Poirier, John T., Mazutis, Linas, Li, Ruifang, Lee, Joo-Hyeon, Amon, Angelika, Rudin, Charles M., Jacks, Tyler, Regev, Aviv, and Tammela, Tuomas

Abstract

Tumor evolution from a single cell into a malignant, heterogeneous tissue remains poorly understood. Here, we profile single-cell transcriptomes of genetically engineered mouse lung tumors at seven stages, from pre-neoplastic hyperplasia to adenocarcinoma. The diversity of transcriptional states increases over time and is reproducible across tumors and mice. Cancer cells progressively adopt alternate lineage identities, computationally predicted to be mediated through a common transitional, high-plasticity cell state (HPCS). Accordingly, HPCS cells prospectively isolated from mouse tumors and human patient-derived xenografts display high capacity for differentiation and proliferation. The HPCS program is associated with poor survival across human cancers and demonstrates chemoresistance in mice. Our study reveals a central principle underpinning intra-tumoral heterogeneity and motivates therapeutic targeting of the HPCS. Cellular states capable of promoting tumor progression and resisting therapies exist in heterogeneous tumors. Marjanovic et al. discover that a high-plasticity cell state common to mouse and human lung tumors drives cellular heterogeneity, is highly tumorigenic and drug resistant, and associates with poor patient prognosis.

Published
2022

36. Single-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations

Author

Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Kalluri, Aditya S., Vellarikkal, Shamsudheen K., Edelman, Elazer R., Nguyen, Lan, Subramanian, Ayshwarya, Ellinor, Patrick T., Regev, Aviv, Kathiresan, Sekar, Gupta, Rajat M., Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Kalluri, Aditya S., Vellarikkal, Shamsudheen K., Edelman, Elazer R., Nguyen, Lan, Subramanian, Ayshwarya, Ellinor, Patrick T., Regev, Aviv, Kathiresan, Sekar, and Gupta, Rajat M.

Abstract

Background: The cells that form the arterial wall contribute to multiple vascular diseases. The extent of cellular heterogeneity within these populations has not been fully characterized. Recent advances in single-cell RNA-sequencing make it possible to identify and characterize cellular subpopulations. Methods: We validate a method for generating a droplet-based single-cell atlas of gene expression in a normal blood vessel. Enzymatic dissociation of 4 whole mouse aortas was followed by single-cell sequencing of >10 000 cells. Results: Clustering analysis of gene expression from aortic cells identified 10 populations of cells representing each of the main arterial cell types: fibroblasts, vascular smooth muscle cells, endothelial cells (ECs), and immune cells, including monocytes, macrophages, and lymphocytes. The most significant cellular heterogeneity was seen in the 3 distinct EC populations. Gene set enrichment analysis of these EC subpopulations identified a lymphatic EC cluster and 2 other populations more specialized in lipoprotein handling, angiogenesis, and extracellular matrix production. These subpopulations persist and exhibit similar changes in gene expression in response to a Western diet. Immunofluorescence for Vcam1 and Cd36 demonstrates regional heterogeneity in EC populations throughout the aorta. Conclusions: We present a comprehensive single-cell atlas of all cells in the aorta. By integrating expression from >1900 genes per cell, we are better able to characterize cellular heterogeneity compared with conventional approaches. Gene expression signatures identify cell subpopulations with vascular disease-relevant functions.

Published
2022

37. Single-nucleus cross-tissue molecular reference maps toward understanding disease gene function

Author

Eraslan, Gökcen, primary, Drokhlyansky, Eugene, additional, Anand, Shankara, additional, Fiskin, Evgenij, additional, Subramanian, Ayshwarya, additional, Slyper, Michal, additional, Wang, Jiali, additional, Van Wittenberghe, Nicholas, additional, Rouhana, John M., additional, Waldman, Julia, additional, Ashenberg, Orr, additional, Lek, Monkol, additional, Dionne, Danielle, additional, Win, Thet Su, additional, Cuoco, Michael S., additional, Kuksenko, Olena, additional, Tsankov, Alexander M., additional, Branton, Philip A., additional, Marshall, Jamie L., additional, Greka, Anna, additional, Getz, Gad, additional, Segrè, Ayellet V., additional, Aguet, François, additional, Rozenblatt-Rosen, Orit, additional, Ardlie, Kristin G., additional, and Regev, Aviv, additional

Published
2022
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38. High-resolution Slide-seqV2 spatial transcriptomics enables discovery of disease-specific cell neighborhoods and pathways

Author

Marshall, Jamie L., primary, Noel, Teia, additional, Wang, Qingbo S., additional, Chen, Haiqi, additional, Murray, Evan, additional, Subramanian, Ayshwarya, additional, Vernon, Katherine A., additional, Bazua-Valenti, Silvana, additional, Liguori, Katie, additional, Keller, Keith, additional, Stickels, Robert R., additional, McBean, Breanna, additional, Heneghan, Rowan M., additional, Weins, Astrid, additional, Macosko, Evan Z., additional, Chen, Fei, additional, and Greka, Anna, additional

Published
2022
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39. Tim-3 adapter protein Bat3 acts as an endogenous regulator of tolerogenic dendritic cell function

Author

Tang, Ruihan, primary, Acharya, Nandini, additional, Subramanian, Ayshwarya, additional, Purohit, Vinee, additional, Tabaka, Marcin, additional, Hou, Yu, additional, He, Danyang, additional, Dixon, Karen O., additional, Lambden, Connor, additional, Xia, Junrong, additional, Rozenblatt-Rosen, Orit, additional, Sobel, Raymond A., additional, Wang, Chao, additional, Regev, Aviv, additional, Anderson, Ana C., additional, and Kuchroo, Vijay K., additional

Published
2022
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40. Multivariable association discovery in population-scale meta-omics studies

Author

Mallick, Himel, primary, Rahnavard, Ali, additional, McIver, Lauren J., additional, Ma, Siyuan, additional, Zhang, Yancong, additional, Nguyen, Long H., additional, Tickle, Timothy L., additional, Weingart, George, additional, Ren, Boyu, additional, Schwager, Emma H., additional, Chatterjee, Suvo, additional, Thompson, Kelsey N., additional, Wilkinson, Jeremy E., additional, Subramanian, Ayshwarya, additional, Lu, Yiren, additional, Waldron, Levi, additional, Paulson, Joseph N., additional, Franzosa, Eric A., additional, Bravo, Hector Corrada, additional, and Huttenhower, Curtis, additional

Published
2021
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42. High Resolution Slide-seqV2 Spatial Transcriptomics Enables Discovery of Disease-Specific Cell Neighborhoods and Pathways

Author

Marshall, Jamie L., primary, Noel, Teia, additional, Wang, Qingbow S., additional, Bazua-Valenti, Silvana, additional, Chen, Haiqi, additional, Murray, Evan, additional, Subramanian, Ayshwarya, additional, Vernon, Katherine A., additional, Liguori, Katie, additional, Keller, Keith, additional, Stickels, Robert R., additional, McBean, Breanna, additional, Heneghan, Rowan M., additional, Weins, Astrid, additional, Macosko, Evan Z., additional, Chen, Fei, additional, and Greka, Anna, additional

Published
2021
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43. A High-Content Screen for Mucin-1-Reducing Compounds Identifies Fostamatinib as a Candidate for Rapid Repurposing for Acute Lung Injury

Author

Kost-Alimova, Maria, Sidhom, Eriene-Heidi, Satyam, Abhigyan, Chamberlain, Brian T., Dvela-Levitt, Moran, Melanson, Michelle, Alper, Seth L., Santos, Jean, Gutierrez, Juan, Subramanian, Ayshwarya, Byrne, Patrick J., Grinkevich, Elizabeth, Reyes-Bricio, Estefanía, Kim, Choah, Clark, Abbe R., Watts, Andrew J.B., Thompson, Rebecca, Marshall, Jamie, Pablo, Juan Lorenzo, Coraor, Juliana, Roignot, Julie, Vernon, Katherine A., Keller, Keith, Campbell, Alissa, Emani, Maheswarareddy, Racette, Matthew, Bazua-Valenti, Silvana, Padovano, Valeria, Weins, Astrid, McAdoo, Stephen P., Tam, Frederick W.K., Ronco, Luciene, Wagner, Florence, Tsokos, George C., Shaw, Jillian L., and Greka, Anna

Published
2020
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44. Single-nucleus cross-tissue molecular reference maps to decipher disease gene function

Author

Eraslan, Gokcen, primary, Drokhlyansky, Eugene, additional, Anand, Shankara, additional, Subramanian, Ayshwarya, additional, Fiskin, Evgenij, additional, Slyper, Michal, additional, Wang, Jiali, additional, Wittenberghe, Nicholas Van, additional, Rouhana, John M., additional, Waldman, Julia, additional, Ashenberg, Orr, additional, Dionne, Danielle, additional, Win, Thet Su, additional, Cuoco, Michael S., additional, Kuksenko, Olena, additional, Branton, Philip A., additional, Marshall, Jamie L., additional, Greka, Anna, additional, Getz, Gad, additional, Segrè, Ayellet V., additional, Aguet, François, additional, Rozenblatt-Rosen, Orit, additional, Ardlie, Kristin G., additional, and Regev, Aviv, additional

Published
2021
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45. ImmGen at 15

Author

Aguilar, Stephanie Vargas, Aguilar, Oscar, Allan, Rhys, Amir, El Ad David, Angeli, Veronique, Artyomov, Maxim, Asinovski, Natasha, Astarita, Jilian, Austen, K. Frank, Bajpai, Geetika, Barrett, Nora, Baysoy, Alev, Benoist, Christophe, Bellemare-Pelletier, Angelique, Berg, Brad, Best, Adam, Bezman, Natalie, Blair, David, Blander, Julie, Bogunovic, Milena, Brennan, Patrick, Brenner, Michael, Brown, Brian, Buechler, Matthew, Buenrostro, Jason, Casanova, Maria Acebes, Choi, Kyunghee, Chow, Andrew, Chudnovskiy, Aleksey, Cipoletta, Daniela, Cohen, Nadia, Collins, James, Colonna, Marco, Cook, Alison, Costello, James, Cremasco, Viviana, Crowl, Ty, Crozat, Karine, Cruse, Richard, D’angelo, June, Dalod, Marc, Davis, Scott, Demiralp, Cagatay, Deng, Tianda, Desai, Jigar, Desland, Fiona, Dhainaut, Maxime, Ding, Jiarui, Doedens, Andrew, Dominguez, Claudia, Doran, Graeme, Dress, Regine, Dustin, Michael, Dwyer, Daniel, Dzhagalov, Ivan, Elpek, Kutlu, Ergun, Ayla, Ericson, Jeff, Esomonu, Eunice, Fairfax, Keke, Fletcher, Anne, Frascoli, Michela, Fuchs, Anja, Gainullina, Anastasiia, Gal-Oz, Shani, Gallagher, Michael, Gautier, Emmanuel, Gazit, Roi, Gibbings, Sophie, Giraud, Matthieu, Ginhoux, Florent, Goldrath, Ananda, Gotthardt, Dagmar, Gray, Daniel, Greter, Melanie, Grieshaber-Bouyer, Ricardo, Guilliams, Martin, Haidermota, Sara, Hardy, Randy, Hashimoto, Daigo, Helft, Julie, Hendricks, Deborah, Heng, Tracy, Hill, Jonathan, Hyatt, Gordon, Idoyaga, Juliana, Jakubzick, Claudia, Jarjoura, Jessica, Jepson, Daniel, Jia, Baosen, Jianu, Radu, Johanson, Tim, Jordan, Stefan, Jojic, Vladimir, Kamimura, Yosuke, Kana, Veronica, Kang, Joonsoo, Kapoor, Varun, Kenigsberg, Ephriam, Kent, Andrew, Kim, Charles, Kim, Edy, Kim, Francis, Kim, Joel, Kim, Kiwook, Kiner, Evgeny, Knell, Jamie, Koller, Daphne, Kozinn, Larry, Krchma, Karen, Kreslavsky, Taras, Kronenberg, Mitchell, Kwan, Wing-Hong, Laidlaw, David, Lam, Viola, Lanier, Lewis, Laplace, Catherine, Lareau, Caleb, Lavin, Yonit, Lavine, Kory, Leader, Andrew, Leboeuf, Marylene, Lee, Jacob, Lee, Jisu, Li, Bo, Li, Hu, Li, Yuesheng, Lionakis, Michail, Luche, Herve, Lynch, Lydia, Magen, Assaf, Maier, Barbara, Malhotra, Deepali, Malhotra, Nidhi, Malissen, Marie, Maslova, Alexandra, Mathis, Diane, Mcfarland, Adelle, Merad, Miriam, Meunier, Etienne, Miller, Jennifer, Milner, Justin, Mingueneau, Michael, Min-Oo, Gundula, Monach, Paul, Moodley, Devapregasan, Mortha, Arthur, Morvan, Maelig, Mostafavi, Sara, Muller, Soren, Muus, Christoph, Nabekura, Tsukasa, Rao, Tata Nageswara, Narang, Vipin, Narayan, Kavitha, Ner-Gaon, Hadas, Nguyen, Quyhn, Nigrovic, Peter, Novakovsky, German, Nutt, Stephan, Omilusik, Kayla, Ortiz-Lopez, Adriana, Paidassi, Helena, Paik, Henry, Painter, Michio, Paynich, Mallory, Peng, Vincent, Potempa, Marc, Pradhan, Rachana, Price, Jeremy, Qi, Yilin, Qi, Yiqing, Quon, Sara, Ramirez, Ricardo, Ramanan, Deepshika, Randolph, Gwendalyn, Regev, Aviv, Rhoads, Andrew, Robinette, Michelle, Rose, Samuel, Rossi, Derrick, Rothamel, Katie, Sachidanandam, Ravi, Sathe, Priyanka, Scott, Charlotte, Seddu, Kumba, See, Peter, Sergushichev, Alexey, Shaw, Laura, Shay, Tal, Shemesh, Avishai, Shinton, Susan, Shyer, Justin, Sieweke, Michael, Smillie, Chris, Spel, Lotte, Spidale, Nick, Stifano, Giuseppina, Subramanian, Ayshwarya, Sun, Joseph, Sylvia, Katelyn, Tellier, Julie, This, Sébastien, Tomasello, Elena, Todorov, Helena, Turley, Shannon, Vijaykumar, Brinda, Wagers, Amy, Wakamatsu, Ei, Wang, Chendi, Wang, Peter, Wroblewska, Aleksandra, Wu, Jun, Yang, Edward, Yang, Liang, Yim, Aldrin, Yng, Lim Sheau, Yoshida, Hideyuki, Yu, Bingfei, Zhou, Yan, Zhu, Yanan, Ziemkiewicz, Caroline, Microenvironment, Cell Differentiation, Immunology and Cancer (MICMAC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The Walter and Eliza Hall Institute of Medical Research (WEHI), Icahn School of Medicine at Mount Sinai [New York] (MSSM), National University of Singapore (NUS), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Harvard Medical School [Boston] (HMS), Genentech, Inc. [San Francisco], Brigham & Women’s Hospital [Boston] (BWH), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Brown University, Lymphocytes B effecteurs et à mémoire – Effector and memory B cells, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Technische Universität Dresden = Dresden University of Technology (TU Dresden), Crozat, Karine, and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
0301 basic medicine, Regulation of gene expression, [SDV.IMM] Life Sciences [q-bio]/Immunology, Test data generation, Computer science, [SDV]Life Sciences [q-bio], Immunology, Gene regulatory network, Genomics, Genome project, Data science, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, microRNA, Immunology and Allergy, DECIPHER, [SDV.IMM]Life Sciences [q-bio]/Immunology, Scientific publishing, ComputingMilieux_MISCELLANEOUS, 030215 immunology
Abstract

International audience; 700 comment | SERIES ImmGen at 15 Nature Immunology's 20 th anniversary is a good opportunity to reminisce about the ImmGen collective endeavor-its goals, successes and horror stories-and the group's exploration of various modes of scientific publishing. The Immunological Genome Project T he Immunological Genome Project (ImmGen) is a collaborative group of immunology and computational biology laboratories that perform a thorough dissection of gene expression and its regulation in the immune system of the mouse. This activity first centered on mRNA expression and then expanded to microRNA (miRNA), chromatin structure, nuclear organization and protein-RNA relationships. Shared protocols, data generation and QC pipelines have yielded data that can be directly compared from >250 stem, lymphoid and myeloid cell types, at baseline or under challenge. The group develops and applies computational tools to decipher regulatory connections and transcriptional control. From its inception, data generated by ImmGen were meant to be a public resource, and they can be accessed through dedicated web and smartphone platforms that use interactive graphic displays that make the results intuitive to users.

Published
2020
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46. Single-Cell Analysis of the Normal Mouse Aorta Reveals Functionally Distinct Endothelial Cell Populations

Author

Kalluri, Aditya S, Vellarikkal, Shamsudheen K, Edelman, Elazer R, Nguyen, Lan, Subramanian, Ayshwarya, Ellinor, Patrick T, Regev, Aviv, Kathiresan, Sekar, Gupta, Rajat M, Kalluri, Aditya S, Vellarikkal, Shamsudheen K, Edelman, Elazer R, Nguyen, Lan, Subramanian, Ayshwarya, Ellinor, Patrick T, Regev, Aviv, Kathiresan, Sekar, and Gupta, Rajat M

Abstract

Background: The cells that form the arterial wall contribute to multiple vascular diseases. The extent of cellular heterogeneity within these populations has not been fully characterized. Recent advances in single-cell RNA-sequencing make it possible to identify and characterize cellular subpopulations. Methods: We validate a method for generating a droplet-based single-cell atlas of gene expression in a normal blood vessel. Enzymatic dissociation of 4 whole mouse aortas was followed by single-cell sequencing of >10 000 cells. Results: Clustering analysis of gene expression from aortic cells identified 10 populations of cells representing each of the main arterial cell types: fibroblasts, vascular smooth muscle cells, endothelial cells (ECs), and immune cells, including monocytes, macrophages, and lymphocytes. The most significant cellular heterogeneity was seen in the 3 distinct EC populations. Gene set enrichment analysis of these EC subpopulations identified a lymphatic EC cluster and 2 other populations more specialized in lipoprotein handling, angiogenesis, and extracellular matrix production. These subpopulations persist and exhibit similar changes in gene expression in response to a Western diet. Immunofluorescence for Vcam1 and Cd36 demonstrates regional heterogeneity in EC populations throughout the aorta. Conclusions: We present a comprehensive single-cell atlas of all cells in the aorta. By integrating expression from >1900 genes per cell, we are better able to characterize cellular heterogeneity compared with conventional approaches. Gene expression signatures identify cell subpopulations with vascular disease-relevant functions.

Published
2021

47. Obesity-instructed TREM2high macrophages identified by comparative analysis of diabetic mouse and human kidney at single cell resolution

Author

Subramanian, Ayshwarya, primary, Vernon, Katherine, additional, Zhou, Yiming, additional, Marshall, Jamie L., additional, Alimova, Maria, additional, Zhang, Fan, additional, Slyper, Michal, additional, Waldman, Julia, additional, Montesinos, Monica S., additional, Dionne, Danielle, additional, Nguyen, Lan T., additional, Cuoco, Michael S., additional, Dubinsky, Dan, additional, Purnell, Jason, additional, Heller, Keith, additional, Sturner, Samuel H., additional, Grinkevich, Elizabeth, additional, Ghoshal, Ayan, additional, Weins, Astrid, additional, Villani, Alexandra-Chloe, additional, Chang, Steven L., additional, Rosenblatt-Rosen, Orit, additional, Shaw, Jillian L., additional, Regev, Aviv, additional, and Greka, Anna, additional

Published
2021
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48. Parental-fetal interplay of immune genes leads to intrauterine growth restriction

Author

Kaur, Gurman, primary, Porter, Caroline B. M., additional, Ashenberg, Orr, additional, Lee, Jack, additional, Riesenfeld, Samantha J., additional, Hofree, Matan, additional, Aggelakopoulou, Maria, additional, Subramanian, Ayshwarya, additional, Kuttikkatte, Subita Balaram, additional, Attfield, Kathrine E., additional, Desel, Christiane A. E., additional, Davies, Jessica L., additional, Evans, Hayley G., additional, Avraham-Davidi, Inbal, additional, Nguyen, Lan T., additional, Dionne, Danielle A., additional, Neumann, Anna E., additional, Jensen, Lise Torp, additional, Barber, Thomas R., additional, Soilleux, Elizabeth, additional, Carrington, Mary, additional, McVean, Gil, additional, Rozenblatt-Rosen, Orit, additional, Regev, Aviv, additional, and Fugger, Lars, additional

Published
2021
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49. A single-cell and spatial atlas of autopsy tissues reveals pathology and cellular targets of SARS-CoV-2

Author

Delorey, Toni M., primary, Ziegler, Carly G. K., additional, Heimberg, Graham, additional, Normand, Rachelly, additional, Yang, Yiming, additional, Segerstolpe, Asa, additional, Abbondanza, Domenic, additional, Fleming, Stephen J., additional, Subramanian, Ayshwarya, additional, Montoro, Daniel T., additional, Jagadeesh, Karthik A., additional, Dey, Kushal K., additional, Sen, Pritha, additional, Slyper, Michal, additional, Pita-Juárez, Yered H., additional, Phillips, Devan, additional, Bloom-Ackerman, Zohar, additional, Barkas, Nick, additional, Ganna, Andrea, additional, Gomez, James, additional, Normandin, Erica, additional, Naderi, Pourya, additional, Popov, Yury V., additional, Raju, Siddharth S., additional, Niezen, Sebastian, additional, Tsai, Linus T.-Y., additional, Siddle, Katherine J., additional, Sud, Malika, additional, Tran, Victoria M., additional, Vellarikkal, Shamsudheen K., additional, Amir-Zilberstein, Liat, additional, Atri, Deepak S., additional, Beechem, Joseph, additional, Brook, Olga R., additional, Chen, Jonathan, additional, Divakar, Prajan, additional, Dorceus, Phylicia, additional, Engreitz, Jesse M., additional, Essene, Adam, additional, Fitzgerald, Donna M., additional, Fropf, Robin, additional, Gazal, Steven, additional, Gould, Joshua, additional, Grzyb, John, additional, Harvey, Tyler, additional, Hecht, Jonathan, additional, Hether, Tyler, additional, Jane-Valbuena, Judit, additional, Leney-Greene, Michael, additional, Ma, Hui, additional, McCabe, Cristin, additional, McLoughlin, Daniel E., additional, Miller, Eric M., additional, Muus, Christoph, additional, Niemi, Mari, additional, Padera, Robert, additional, Pan, Liuliu, additional, Pant, Deepti, additional, Pe’er, Carmel, additional, Pfiffner-Borges, Jenna, additional, Pinto, Christopher J., additional, Plaisted, Jacob, additional, Reeves, Jason, additional, Ross, Marty, additional, Rudy, Melissa, additional, Rueckert, Erroll H., additional, Siciliano, Michelle, additional, Sturm, Alexander, additional, Todres, Ellen, additional, Waghray, Avinash, additional, Warren, Sarah, additional, Zhang, Shuting, additional, Zollinger, Daniel R., additional, Cosimi, Lisa, additional, Gupta, Rajat M., additional, Hacohen, Nir, additional, Hide, Winston, additional, Price, Alkes L., additional, Rajagopal, Jayaraj, additional, Tata, Purushothama Rao, additional, Riedel, Stefan, additional, Szabo, Gyongyi, additional, Tickle, Timothy L., additional, Hung, Deborah, additional, Sabeti, Pardis C., additional, Novak, Richard, additional, Rogers, Robert, additional, Ingber, Donald E., additional, Gordon Jiang, Z., additional, Juric, Dejan, additional, Babadi, Mehrtash, additional, Farhi, Samouil L., additional, Stone, James R., additional, Vlachos, Ioannis S., additional, Solomon, Isaac H., additional, Ashenberg, Orr, additional, Porter, Caroline B.M., additional, Li, Bo, additional, Shalek, Alex K., additional, Villani, Alexandra-Chloé, additional, Rozenblatt-Rosen, Orit, additional, and Regev, Aviv, additional

Published
2021
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50. Abstract 1511: A highly plastic cell state emerges during lung adenocarcinoma evolution

Author

Chan, Jason Earl, primary, Marjanovic, Nemanja Despot, additional, Hofree, Matan, additional, Canner, David, additional, Wu, Katherine, additional, Hartmann, Griffin, additional, Smith, Olivia C., additional, Kim, Jonathan, additional, Hudson, Anna, additional, Subramanian, Ayshwarya, additional, Pitter, Kenneth, additional, Rekhtman, Natasha, additional, Massion, Pierre P., additional, Poirier, John T., additional, Rudin, Charles M., additional, Jacks, Tyler, additional, Regev, Aviv, additional, and Tammela, Tuomas, additional

Published
2020
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