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1. Trimodal single-cell profiling reveals a novel pediatric CD8αα+ T cell subset and broad age-related molecular reprogramming across the T cell compartment

Author

Thomson, Zachary, He, Ziyuan, Swanson, Elliott, Henderson, Katherine, Phalen, Cole, Zaim, Samir Rachid, Pebworth, Mark-Phillip, Okada, Lauren Y., Heubeck, Alexander T., Roll, Charles R., Hernandez, Veronica, Weiss, Morgan, Genge, Palak C., Reading, Julian, Giles, Josephine R., Manne, Sasikanth, Dougherty, Jeanette, Jasen, C. J., Greenplate, Allison R., Becker, Lynne A., Graybuck, Lucas T., Vasaikar, Suhas V., Szeto, Gregory L., Savage, Adam K., Speake, Cate, Buckner, Jane H., Li, Xiao-jun, Bumol, Thomas F., Wherry, E.John, Torgerson, Troy R., Vella, Laura A., Henrickson, Sarah E., Skene, Peter J., and Gustafson, Claire E.

Published
2023
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3. Author Correction: Trimodal single-cell profiling reveals a novel pediatric CD8αα+ T cell subset and broad age-related molecular reprogramming across the T cell compartment

Author

Thomson, Zachary, He, Ziyuan, Swanson, Elliott, Henderson, Katherine, Phalen, Cole, Zaim, Samir Rachid, Pebworth, Mark-Phillip, Okada, Lauren Y., Heubeck, Alexander T., Roll, Charles R., Hernandez, Veronica, Weiss, Morgan, Genge, Palak C., Reading, Julian, Giles, Josephine R., Manne, Sasikanth, Dougherty, Jeanette, Jasen, C. J., Greenplate, Allison R., Becker, Lynne A., Graybuck, Lucas T., Vasaikar, Suhas V., Szeto, Gregory L., Savage, Adam K., Speake, Cate, Buckner, Jane H., Li, Xiao-jun, Bumol, Thomas F., Wherry, E.John, Torgerson, Troy R., Vella, Laura A., Henrickson, Sarah E., Skene, Peter J., and Gustafson, Claire E.

Published
2024
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4. Comparative cellular analysis of motor cortex in human, marmoset and mouse

Author

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

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

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

Published
2021

5. Conserved cell types with divergent features in human versus mouse cortex.

Author

Hodge, Rebecca D, Bakken, Trygve E, Miller, Jeremy A, Smith, Kimberly A, Barkan, Eliza R, Graybuck, Lucas T, Close, Jennie L, Long, Brian, Johansen, Nelson, Penn, Osnat, Yao, Zizhen, Eggermont, Jeroen, Höllt, Thomas, Levi, Boaz P, Shehata, Soraya I, Aevermann, Brian, Beller, Allison, Bertagnolli, Darren, Brouner, Krissy, Casper, Tamara, Cobbs, Charles, Dalley, Rachel, Dee, Nick, Ding, Song-Lin, Ellenbogen, Richard G, Fong, Olivia, Garren, Emma, Goldy, Jeff, Gwinn, Ryder P, Hirschstein, Daniel, Keene, C Dirk, Keshk, Mohamed, Ko, Andrew L, Lathia, Kanan, Mahfouz, Ahmed, Maltzer, Zoe, McGraw, Medea, Nguyen, Thuc Nghi, Nyhus, Julie, Ojemann, Jeffrey G, Oldre, Aaron, Parry, Sheana, Reynolds, Shannon, Rimorin, Christine, Shapovalova, Nadiya V, Somasundaram, Saroja, Szafer, Aaron, Thomsen, Elliot R, Tieu, Michael, Quon, Gerald, Scheuermann, Richard H, Yuste, Rafael, Sunkin, Susan M, Lelieveldt, Boudewijn, Feng, David, Ng, Lydia, Bernard, Amy, Hawrylycz, Michael, Phillips, John W, Tasic, Bosiljka, Zeng, Hongkui, Jones, Allan R, Koch, Christof, and Lein, Ed S

Subjects
Cerebral Cortex, Astrocytes, Neurons, Animals, Humans, Mice, Species Specificity, Neural Inhibition, Principal Component Analysis, Adolescent, Adult, Aged, Middle Aged, Female, Male, Young Adult, Biological Evolution, Single-Cell Analysis, Transcriptome, RNA-Seq, Genetics, Neurosciences, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Aetiology, Underpinning research, Neurological, General Science & Technology
Abstract

Elucidating the cellular architecture of the human cerebral cortex is central to understanding our cognitive abilities and susceptibility to disease. Here we used single-nucleus RNA-sequencing analysis to perform a comprehensive study of cell types in the middle temporal gyrus of human cortex. We identified a highly diverse set of excitatory and inhibitory neuron types that are mostly sparse, with excitatory types being less layer-restricted than expected. Comparison to similar mouse cortex single-cell RNA-sequencing datasets revealed a surprisingly well-conserved cellular architecture that enables matching of homologous types and predictions of properties of human cell types. Despite this general conservation, we also found extensive differences between homologous human and mouse cell types, including marked alterations in proportions, laminar distributions, gene expression and morphology. These species-specific features emphasize the importance of directly studying human brain.

Published
2019

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

Author

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

Published
2022
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9. Shared and distinct transcriptomic cell types across neocortical areas

Author

Tasic, Bosiljka, Yao, Zizhen, Graybuck, Lucas T., Smith, Kimberly A., Nguyen, Thuc Nghi, Bertagnolli, Darren, and Goldy, Jeff

Subjects
Brain cells -- Research, Neocortex -- Research, RNA sequencing -- Usage, Neurophysiology, GABA, Brain, Neurons, RNA, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The neocortex contains a multitude of cell types that are segregated into layers and functionally distinct areas. To investigate the diversity of cell types across the mouse neocortex, here we analysed 23,822 cells from two areas at distant poles of the mouse neocortex: the primary visual cortex and the anterior lateral motor cortex. We define 133 transcriptomic cell types by deep, single-cell RNA sequencing. Nearly all types of GABA ([gamma]-aminobutyric acid)-containing neurons are shared across both areas, whereas most types of glutamatergic neurons were found in one of the two areas. By combining single-cell RNA sequencing and retrograde labelling, we match transcriptomic types of glutamatergic neurons to their long-range projection specificity. Our study establishes a combined transcriptomic and projectional taxonomy of cortical cell types from functionally distinct areas of the adult mouse cortex. Single-cell transcriptomics of more than 20,000 cells from two functionally distinct areas of the mouse neocortex identifies 133 transcriptomic types, and provides a foundation for understanding the diversity of cortical cell types., Author(s): Bosiljka Tasic [sup.1] , Zizhen Yao [sup.1] , Lucas T. Graybuck [sup.1] , Kimberly A. Smith [sup.1] , Thuc Nghi Nguyen [sup.1] , Darren Bertagnolli [sup.1] , Jeff Goldy [...]

Published
2018
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11. Trimodal single-cell profiling reveals a novel pediatric CD8αα+T cell subset and broad age-related molecular reprogramming across the T cell compartment

Author

Thomson, Zachary, He, Ziyuan, Swanson, Elliott, Henderson, Katherine, Phalen, Cole, Zaim, Samir Rachid, Pebworth, Mark-Phillip, Okada, Lauren Y., Heubeck, Alexander T., Roll, Charles R., Hernandez, Veronica, Weiss, Morgan, Genge, Palak C., Reading, Julian, Giles, Josephine R., Manne, Sasikanth, Dougherty, Jeanette, Jasen, C. J., Greenplate, Allison R., Becker, Lynne A., Graybuck, Lucas T., Vasaikar, Suhas V., Szeto, Gregory L., Savage, Adam K., Speake, Cate, Buckner, Jane H., Li, Xiao-jun, Bumol, Thomas F., Wherry, E.John, Torgerson, Troy R., Vella, Laura A., Henrickson, Sarah E., Skene, Peter J., and Gustafson, Claire E.

Abstract

Age-associated changes in the T cell compartment are well described. However, limitations of current single-modal or bimodal single-cell assays, including flow cytometry, RNA-seq (RNA sequencing) and CITE-seq (cellular indexing of transcriptomes and epitopes by sequencing), have restricted our ability to deconvolve more complex cellular and molecular changes. Here, we profile >300,000 single T cells from healthy children (aged 11–13 years) and older adults (aged 55–65 years) by using the trimodal assay TEA-seq (single-cell analysis of mRNA transcripts, surface protein epitopes and chromatin accessibility), which revealed that molecular programming of T cell subsets shifts toward a more activated basal state with age. Naive CD4+T cells, considered relatively resistant to aging, exhibited pronounced transcriptional and epigenetic reprogramming. Moreover, we discovered a novel CD8αα+T cell subset lost with age that is epigenetically poised for rapid effector responses and has distinct inhibitory, costimulatory and tissue-homing properties. Together, these data reveal new insights into age-associated changes in the T cell compartment that may contribute to differential immune responses.

Published
2023
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12. PALMO: a comprehensive platform for analyzing longitudinal multi-omics data

Author

Vasaikar, Suhas V., primary, Savage, Adam K., additional, Gong, Qiuyu, additional, Swanson, Elliott, additional, Talla, Aarthi, additional, Lord, Cara, additional, Heubeck, Alexander T, additional, Reading, Julian, additional, Graybuck, Lucas T., additional, Meijer, Paul, additional, Torgerson, Troy R., additional, Skene, Peter J., additional, Bumol, Thomas F., additional, and Li, Xiao-jun, additional

Published
2022
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13. Distinct Heterogeneity in the Naive T cell Compartments of Children and Adults

Author

Gustafson, Claire E., primary, Thomson, Zachary, additional, He, Ziyuan, additional, Swanson, Elliott, additional, Henderson, Katherine, additional, Pebworth, Mark-Phillip, additional, Okada, Lauren Y., additional, Heubeck, Alexander T., additional, Roll, Charles R., additional, Hernandez, Veronica, additional, Weiss, Morgan, additional, Genge, Palak C., additional, Reading, Julian, additional, Giles, Josephine R., additional, Manne, Sasikanth, additional, Dougherty, Jeanette, additional, Jasen, CJ, additional, Greenplate, Allison R., additional, Becker, Lynne A., additional, Graybuck, Lucas T., additional, Vasaikar, Suhas V., additional, Szeto, Gregory L., additional, Savage, Adam K., additional, Speake, Cate, additional, Buckner, Jane H., additional, Li, Xiao-jun, additional, Torgerson, Troy R., additional, Wherry, E. John, additional, Bumol, Thomas F., additional, Vella, Laura A., additional, Henrickson, Sarah E., additional, and Skene, Peter J., additional

Published
2022
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14. A Suite of Transgenic Driver and Reporter Mouse Lines with Enhanced Brain-Cell-Type Targeting and Functionality

Author

Daigle, Tanya L., Madisen, Linda, Hage, Travis A., Valley, Matthew T., Knoblich, Ulf, Larsen, Rylan S., Takeno, Marc M., Huang, Lawrence, Gu, Hong, Larsen, Rachael, Mills, Maya, Bosma-Moody, Alice, Siverts, La’ Akea, Walker, Miranda, Graybuck, Lucas T., Yao, Zizhen, Fong, Olivia, Nguyen, Thuc Nghi, Garren, Emma, Lenz, Garreck H., Chavarha, Mariya, Pendergraft, Julie, Harrington, James, Hirokawa, Karla E., Harris, Julie A., Nicovich, Philip R., McGraw, Medea J., Ollerenshaw, Douglas R., Smith, Kimberly A., Baker, Christopher A., Ting, Jonathan T., Sunkin, Susan M., Lecoq, Jérôme, Lin, Michael Z., Boyden, Edward S., Murphy, Gabe J., da Costa, Nuno M., Waters, Jack, Li, Lu, Tasic, Bosiljka, Zeng, Hongkui, Daigle, Tanya L., Madisen, Linda, Hage, Travis A., Valley, Matthew T., Knoblich, Ulf, Larsen, Rylan S., Takeno, Marc M., Huang, Lawrence, Gu, Hong, Larsen, Rachael, Mills, Maya, Bosma-Moody, Alice, Siverts, La’ Akea, Walker, Miranda, Graybuck, Lucas T., Yao, Zizhen, Fong, Olivia, Nguyen, Thuc Nghi, Garren, Emma, Lenz, Garreck H., Chavarha, Mariya, Pendergraft, Julie, Harrington, James, Hirokawa, Karla E., Harris, Julie A., Nicovich, Philip R., McGraw, Medea J., Ollerenshaw, Douglas R., Smith, Kimberly A., Baker, Christopher A., Ting, Jonathan T., Sunkin, Susan M., Lecoq, Jérôme, Lin, Michael Z., Boyden, Edward S., Murphy, Gabe J., da Costa, Nuno M., Waters, Jack, Li, Lu, Tasic, Bosiljka, and Zeng, Hongkui

Abstract

An expanded toolkit of transgenic mouse lines for exploring the organization, function, and development of mammalian neural circuits.

Published
2022

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

Author

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

Abstract

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

Published
2022

16. Single-cell and single-nucleus RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates, and humans

Author

Bakken, Trygve E, primary, van Velthoven, Cindy TJ, additional, Menon, Vilas, additional, Hodge, Rebecca D, additional, Yao, Zizhen, additional, Nguyen, Thuc Nghi, additional, Graybuck, Lucas T, additional, Horwitz, Gregory D, additional, Bertagnolli, Darren, additional, Goldy, Jeff, additional, Yanny, Anna Marie, additional, Garren, Emma, additional, Parry, Sheana, additional, Casper, Tamara, additional, Shehata, Soraya I, additional, Barkan, Eliza R, additional, Szafer, Aaron, additional, Levi, Boaz P, additional, Dee, Nick, additional, Smith, Kimberly A, additional, Sunkin, Susan M, additional, Bernard, Amy, additional, Phillips, John, additional, Hawrylycz, Michael J, additional, Koch, Christof, additional, Murphy, Gabe J, additional, Lein, Ed, additional, Zeng, Hongkui, additional, and Tasic, Bosiljka, additional

Published
2021
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17. Signature morpho-electric, transcriptomic, and dendritic properties of human layer 5 neocortical pyramidal neurons

Author

Kalmbach, Brian E., primary, Hodge, Rebecca D., additional, Jorstad, Nikolas L., additional, Owen, Scott, additional, de Frates, Rebecca, additional, Yanny, Anna Marie, additional, Dalley, Rachel, additional, Mallory, Matt, additional, Graybuck, Lucas T., additional, Radaelli, Cristina, additional, Keene, C. Dirk, additional, Gwinn, Ryder P., additional, Silbergeld, Daniel L., additional, Cobbs, Charles, additional, Ojemann, Jeffrey G., additional, Ko, Andrew L., additional, Patel, Anoop P., additional, Ellenbogen, Richard G., additional, Bakken, Trygve E., additional, Daigle, Tanya L., additional, Dee, Nick, additional, Lee, Brian R., additional, McGraw, Medea, additional, Nicovich, Philip R., additional, Smith, Kimberly, additional, Sorensen, Staci A., additional, Tasic, Bosiljka, additional, Zeng, Hongkui, additional, Koch, Christof, additional, Lein, Ed S., additional, and Ting, Jonathan T., additional

Published
2021
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18. Author response: Single-cell and single-nucleus RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates, and humans

Author

Bakken, Trygve E, primary, van Velthoven, Cindy TJ, additional, Menon, Vilas, additional, Hodge, Rebecca D, additional, Yao, Zizhen, additional, Nguyen, Thuc Nghi, additional, Graybuck, Lucas T, additional, Horwitz, Gregory D, additional, Bertagnolli, Darren, additional, Goldy, Jeff, additional, Yanny, Anna Marie, additional, Garren, Emma, additional, Parry, Sheana, additional, Casper, Tamara, additional, Shehata, Soraya I, additional, Barkan, Eliza R, additional, Szafer, Aaron, additional, Levi, Boaz P, additional, Dee, Nick, additional, Smith, Kimberly A, additional, Sunkin, Susan M, additional, Bernard, Amy, additional, Phillips, John, additional, Hawrylycz, Michael J, additional, Koch, Christof, additional, Murphy, Gabe J, additional, Lein, Ed, additional, Zeng, Hongkui, additional, and Tasic, Bosiljka, additional

Published
2021
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19. A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation

Author

Yao, Zizhen, primary, van Velthoven, Cindy T.J., additional, Nguyen, Thuc Nghi, additional, Goldy, Jeff, additional, Sedeno-Cortes, Adriana E., additional, Baftizadeh, Fahimeh, additional, Bertagnolli, Darren, additional, Casper, Tamara, additional, Chiang, Megan, additional, Crichton, Kirsten, additional, Ding, Song-Lin, additional, Fong, Olivia, additional, Garren, Emma, additional, Glandon, Alexandra, additional, Gouwens, Nathan W., additional, Gray, James, additional, Graybuck, Lucas T., additional, Hawrylycz, Michael J., additional, Hirschstein, Daniel, additional, Kroll, Matthew, additional, Lathia, Kanan, additional, Lee, Changkyu, additional, Levi, Boaz, additional, McMillen, Delissa, additional, Mok, Stephanie, additional, Pham, Thanh, additional, Ren, Qingzhong, additional, Rimorin, Christine, additional, Shapovalova, Nadiya, additional, Sulc, Josef, additional, Sunkin, Susan M., additional, Tieu, Michael, additional, Torkelson, Amy, additional, Tung, Herman, additional, Ward, Katelyn, additional, Dee, Nick, additional, Smith, Kimberly A., additional, Tasic, Bosiljka, additional, and Zeng, Hongkui, additional

Published
2021
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20. Longitudinal immune dynamics of mild COVID-19 define signatures of recovery and persistence

Author

Talla, Aarthi, primary, Vasaikar, Suhas V., additional, Lemos, Maria P., additional, Moodie, Zoe, additional, Lee Pebworth, Mark-Phillip, additional, Henderson, Kathy E., additional, Cohen, Kristen W., additional, Czartoski, Julie L., additional, Lai, Lilin, additional, Suthar, Mehul S., additional, Heubeck, Alexander T, additional, Genge, Palak C., additional, Roll, Charles R., additional, Weiss, Morgan, additional, Reading, Julian, additional, Kondza, Nina, additional, MacMillan, Hugh, additional, Fong, Olivia C., additional, Thomson, Zachary James, additional, Graybuck, Lucas T., additional, Okada, Lauren Y., additional, Newell, Evan W., additional, Coffey, Ernest M., additional, Meijer, Paul, additional, Becker, Lynne A., additional, De Rosa, Stephen C., additional, Skene, Peter J., additional, Torgerson, Troy R., additional, Li, Xiao-jun, additional, Szeto, Gregory Lee, additional, McElrath, M. Juliana, additional, and Bumol, Thomas F., additional

Published
2021
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21. Enhancer viruses for combinatorial cell-subclass-specific labeling

Author

Graybuck, Lucas T., primary, Daigle, Tanya L., additional, Sedeño-Cortés, Adriana E., additional, Walker, Miranda, additional, Kalmbach, Brian, additional, Lenz, Garreck H., additional, Morin, Elyse, additional, Nguyen, Thuc Nghi, additional, Garren, Emma, additional, Bendrick, Jacqueline L., additional, Kim, Tae Kyung, additional, Zhou, Thomas, additional, Mortrud, Marty, additional, Yao, Shenqin, additional, Siverts, La’ Akea, additional, Larsen, Rachael, additional, Gore, Bryan B., additional, Szelenyi, Eric R., additional, Trader, Cameron, additional, Balaram, Pooja, additional, van Velthoven, Cindy T.J., additional, Chiang, Megan, additional, Mich, John K., additional, Dee, Nick, additional, Goldy, Jeff, additional, Cetin, Ali H., additional, Smith, Kimberly, additional, Way, Sharon W., additional, Esposito, Luke, additional, Yao, Zizhen, additional, Gradinaru, Viviana, additional, Sunkin, Susan M., additional, Lein, Ed, additional, Levi, Boaz P., additional, Ting, Jonathan T., additional, Zeng, Hongkui, additional, and Tasic, Bosiljka, additional

Published
2021
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22. Simultaneous trimodal single-cell measurement of transcripts, epitopes, and chromatin accessibility using TEA-seq

Author

Swanson, Elliott, primary, Lord, Cara, additional, Reading, Julian, additional, Heubeck, Alexander T, additional, Genge, Palak C, additional, Thomson, Zachary, additional, Weiss, Morgan DA, additional, Li, Xiao-jun, additional, Savage, Adam K, additional, Green, Richard R, additional, Torgerson, Troy R, additional, Bumol, Thomas F, additional, Graybuck, Lucas T, additional, and Skene, Peter J, additional

Published
2021
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23. Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex

Author

Mich, John K., primary, Graybuck, Lucas T., additional, Hess, Erik E., additional, Mahoney, Joseph T., additional, Kojima, Yoshiko, additional, Ding, Yi, additional, Somasundaram, Saroja, additional, Miller, Jeremy A., additional, Kalmbach, Brian E., additional, Radaelli, Cristina, additional, Gore, Bryan B., additional, Weed, Natalie, additional, Omstead, Victoria, additional, Bishaw, Yemeserach, additional, Shapovalova, Nadiya V., additional, Martinez, Refugio A., additional, Fong, Olivia, additional, Yao, Shenqin, additional, Mortrud, Marty, additional, Chong, Peter, additional, Loftus, Luke, additional, Bertagnolli, Darren, additional, Goldy, Jeff, additional, Casper, Tamara, additional, Dee, Nick, additional, Opitz-Araya, Ximena, additional, Cetin, Ali, additional, Smith, Kimberly A., additional, Gwinn, Ryder P., additional, Cobbs, Charles, additional, Ko, Andrew L., additional, Ojemann, Jeffrey G., additional, Keene, C. Dirk, additional, Silbergeld, Daniel L., additional, Sunkin, Susan M., additional, Gradinaru, Viviana, additional, Horwitz, Gregory D., additional, Zeng, Hongkui, additional, Tasic, Bosiljka, additional, Lein, Ed S., additional, Ting, Jonathan T., additional, and Levi, Boaz P., additional

Published
2021
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24. Author response: Simultaneous trimodal single-cell measurement of transcripts, epitopes, and chromatin accessibility using TEA-seq

Author

Swanson, Elliott, primary, Lord, Cara, additional, Reading, Julian, additional, Heubeck, Alexander T, additional, Genge, Palak C, additional, Thomson, Zachary, additional, Weiss, Morgan DA, additional, Li, Xiao-jun, additional, Savage, Adam K, additional, Green, Richard R, additional, Torgerson, Troy R, additional, Bumol, Thomas F, additional, Graybuck, Lucas T, additional, and Skene, Peter J, additional

Published
2021
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25. Single-cell RNA-seq uncovers shared and distinct axes of variation in dorsal LGN neurons in mice, non-human primates and humans

Author

Bakken, Trygve E., primary, van Velthoven, Cindy T.J., additional, Menon, Vilas, additional, Hodge, Rebecca D., additional, Yao, Zizhen, additional, Nguyen, Thuc Nghi, additional, Graybuck, Lucas T., additional, Horwitz, Gregory D., additional, Bertagnolli, Darren, additional, Goldy, Jeff, additional, Garren, Emma, additional, Parry, Sheana, additional, Casper, Tamara, additional, Shehata, Soraya I., additional, Barkan, Eliza R., additional, Szafer, Aaron, additional, Levi, Boaz P., additional, Dee, Nick, additional, Smith, Kimberly A., additional, Sunkin, Susan M., additional, Bernard, Amy, additional, Phillips, John W., additional, Hawrylycz, Michael, additional, Koch, Christof, additional, Murphy, Gabe, additional, Lein, Ed, additional, Zeng, Hongkui, additional, and Tasic, Bosiljka, additional

Published
2020
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27. Distinct Transcriptomic Cell Types and Neural Circuits of the Subiculum and Prosubiculum along the Dorsal-Ventral Axis

Author

Ding, Song-Lin, primary, Yao, Zizhen, additional, Hirokawa, Karla E., additional, Nguyen, Thuc Nghi, additional, Graybuck, Lucas T., additional, Fong, Olivia, additional, Bohn, Phillip, additional, Ngo, Kiet, additional, Smith, Kimberly A., additional, Koch, Christof, additional, Phillips, John W., additional, Lein, Ed S., additional, Harris, Julie A., additional, Tasic, Bosiljka, additional, and Zeng, Hongkui, additional

Published
2020
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28. Evolution of cellular diversity in primary motor cortex of human, marmoset monkey, and mouse

Author

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

Published
2020
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29. A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation

Author

Yao, Zizhen, primary, Nguyen, Thuc Nghi, additional, van Velthoven, Cindy T. J., additional, Goldy, Jeff, additional, Sedeno-Cortes, Adriana E., additional, Baftizadeh, Fahimeh, additional, Bertagnolli, Darren, additional, Casper, Tamara, additional, Crichton, Kirsten, additional, Ding, Song-Lin, additional, Fong, Olivia, additional, Garren, Emma, additional, Glandon, Alexandra, additional, Gray, James, additional, Graybuck, Lucas T., additional, Hirschstein, Daniel, additional, Kroll, Matthew, additional, Lathia, Kanan, additional, Levi, Boaz, additional, McMillen, Delissa, additional, Mok, Stephanie, additional, Pham, Thanh, additional, Ren, Qingzhong, additional, Rimorin, Christine, additional, Shapovalova, Nadiya, additional, Sulc, Josef, additional, Sunkin, Susan M., additional, Tieu, Michael, additional, Torkelson, Amy, additional, Tung, Herman, additional, Ward, Katelyn, additional, Dee, Nick, additional, Smith, Kimberly A., additional, Tasic, Bosiljka, additional, and Zeng, Hongkui, additional

Published
2020
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30. Functional Enhancer Elements Drive Subclass-Selective Expression from Mouse to Primate Neocortex

Author

Mich, John K., primary, Graybuck, Lucas T., additional, Hess, Erik, additional, Mahoney, Joseph, additional, Kojima, Yoshiko, additional, Ding, Yi, additional, Somasundaram, Saroja, additional, Miller, Jeremy A., additional, Weed, Natalie, additional, Omstead, Victoria, additional, Bishaw, Yemeserach, additional, Shapovalova, Nadiya, additional, Martinez, Refugio, additional, Fong, Olivia, additional, Yao, Shenqin, additional, Mortrud, Marty, additional, Chong, Peter, additional, Loftus, Luke, additional, Bertagnolli, Darren, additional, Goldy, Jeff, additional, Casper, Tamara, additional, Dee, Nick, additional, Opitz-Araya, Ximena, additional, Cetin, Ali, additional, Smith, Kimberly A., additional, Gwinn, Ryder P., additional, Cobbs, Charles, additional, Ko, Andrew L., additional, Ojemann, Jeffrey G., additional, Keene, C. Dirk, additional, Silbergeld, Daniel L., additional, Sunkin, Susan M., additional, Gradinaru, Viviana, additional, Horwitz, Gregory D., additional, Zeng, Hongkui, additional, Tasic, Bosiljka, additional, Lein, Ed, additional, Ting, Jonathan, additional, and Levi, Boaz, additional

Published
2020
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31. Distinct transcriptomic cell types and neural circuits of the subiculum and prosubiculum along the dorsal-ventral axis

Author

Ding, Song-Lin, primary, Yao, Zizhen, additional, Hirokawa, Karla E., additional, Nguyen, Thuc Nghi, additional, Graybuck, Lucas T., additional, Fong, Olivia, additional, Bohn, Phillip, additional, Ngo, Kiet, additional, Smith, Kimberly A., additional, Koch, Christof, additional, Phillips, John W., additional, Lein, Ed S., additional, Harris, Julie A., additional, Tasic, Bosiljka, additional, and Zeng, Hongkui, additional

Published
2019
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32. Single-cell transcriptomic evidence for dense intracortical neuropeptide networks

Author

Smith, Stephen J, primary, Sümbül, Uygar, additional, Graybuck, Lucas T, additional, Collman, Forrest, additional, Seshamani, Sharmishtaa, additional, Gala, Rohan, additional, Gliko, Olga, additional, Elabbady, Leila, additional, Miller, Jeremy A, additional, Bakken, Trygve E, additional, Rossier, Jean, additional, Yao, Zizhen, additional, Lein, Ed, additional, Zeng, Hongkui, additional, Tasic, Bosiljka, additional, and Hawrylycz, Michael, additional

Published
2019
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33. Author response: Single-cell transcriptomic evidence for dense intracortical neuropeptide networks

Author

Smith, Stephen J, primary, Sümbül, Uygar, additional, Graybuck, Lucas T, additional, Collman, Forrest, additional, Seshamani, Sharmishtaa, additional, Gala, Rohan, additional, Gliko, Olga, additional, Elabbady, Leila, additional, Miller, Jeremy A, additional, Bakken, Trygve E, additional, Rossier, Jean, additional, Yao, Zizhen, additional, Lein, Ed, additional, Zeng, Hongkui, additional, Tasic, Bosiljka, additional, and Hawrylycz, Michael, additional

Published
2019
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34. Epigenetic landscape and AAV targeting of human neocortical cell classes

Author

Mich, John K., Hess, Erik E., Graybuck, Lucas T., Somasundaram, Saroja, Miller, Jeremy A., Ding, Yi, Shapovalova, Nadiya V., Fong, Olivia, Yao, Shenqin, Mortrud, Marty, Chong, Peter, Bertagnolli, Darren, Goldy, Jeff, Casper, Tamara, Kroll, Matthew, Hodge, Rebecca D., Bakken, Trygve E., Yao, Zizhen, Dee, Nick, Cetin, Ali, Smith, Kimberly A., Gwinn, Ryder P., Cobbs, Charles, Ko, Andrew. L., Ojemann, Jeffrey G., Keene, C. Dirk, Silbergeld, Daniel. L., Gradinaru, Viviana, Sunkin, Susan M., Zeng, Hongkui, Lein, Ed S., Tasic, Bosiljka, Ting, Jonathan T., and Levi, Boaz P.

Abstract

Myriad cell types comprise the human neocortex, but their roles in normal brain function and disease are largely unknown because few tools exist. To find enhancer elements useful for cell type-specific genetic tools, we examined chromatin accessibility in >2,800 high-quality single human neocortical nuclei. Accessible elements frequently are conserved in mouse (34%), often overlap with hypomethylated sites (27%), and connect cell types with neurological diseases via trait-associated SNPs. Directly testing these elements in viral vectors demonstrates functional enhancer activity with cell type specificity predicted by their chromatin accessibility patterns. In summary we present a catalog of human cell class-specific epigenetic elements, and utilize them for new species-agnostic cell type-specific viral genetic tools, which will illuminate human neuron function and drive gene therapy applications. One sentence summary Mapping chromatin accessibility in human brain cell classes links gene regulation to disease and enables human genetic tools.

Published
2019
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35. Prospective, brain-wide labeling of neuronal subclasses with enhancer-driven AAVs

Author

Graybuck, Lucas T., Sedeño-Cortés, Adriana E., Nguyen, Thuc Nghi, Walker, Miranda, Szelenyi, Eric, Lenz, Garreck, Sieverts, La’Akea, Kim, Tae Kyung, Garren, Emma, Kalmbach, Brian, Yao, Shenqin, Mortrud, Marty, Mich, John, Goldy, Jeff, Smith, Kimberly, Dee, Nick, Yao, Zizhen, Cetin, Ali, Levi, Boaz, Lein, Ed, Ting, Jonathan, Zeng, Hongkui, Daigle, Tanya, and Tasic, Bosiljka

Abstract

Labeling and perturbation of specific cell types in multicellular systems has transformed our ability to understand them. The rapid pace of cell type identification by new single-cell analysis methods has not been met with efficient access to these newly discovered types. To enable access to specific neural populations in the mouse cortex, we have collected single cell chromatin accessibility data from select cell types. We clustered the single cell data and mapped them to single cell transcriptomics to identify highly specific enhancers for cell subclasses. These enhancers, when cloned into AAVs and delivered to the brain by retro orbital injections, transgene expression in specific cell subclasses throughout the mouse brain. This approach will enable functional investigation of cell types in the mouse cortex and beyond. One sentence Summary Combining scATAC-seq and scRNA-seq identifies subclass-specific enhancers to label cells in mouse cortex at high resolution

Published
2019
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36. Multimodal Analysis of Cell Types in a Hypothalamic Node Controlling Social Behavior

Author

Kim, Dong-Wook, primary, Yao, Zizhen, additional, Graybuck, Lucas T., additional, Kim, Tae Kyung, additional, Nguyen, Thuc Nghi, additional, Smith, Kimberly A., additional, Fong, Olivia, additional, Yi, Lynn, additional, Koulena, Noushin, additional, Pierson, Nico, additional, Shah, Sheel, additional, Lo, Liching, additional, Pool, Allan-Hermann, additional, Oka, Yuki, additional, Pachter, Lior, additional, Cai, Long, additional, Tasic, Bosiljka, additional, Zeng, Hongkui, additional, and Anderson, David J., additional

Published
2019
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37. Functional enhancer elements drive subclass-selective expression from mouse to primate neocortex

Author

Mich, John K., primary, Graybuck, Lucas T., additional, Hess, Erik E., additional, Mahoney, Joseph T., additional, Kojima, Yoshiko, additional, Ding, Yi, additional, Somasundaram, Saroja, additional, Miller, Jeremy A., additional, Weed, Natalie, additional, Omstead, Victoria, additional, Bishaw, Yemeserach, additional, Shapovalova, Nadiya V., additional, Martinez, Refugio A., additional, Fong, Olivia, additional, Yao, Shenqin, additional, Mortrud, Marty, additional, Chong, Peter, additional, Loftus, Luke, additional, Bertagnolli, Darren, additional, Goldy, Jeff, additional, Casper, Tamara, additional, Dee, Nick, additional, Opitz-Araya, Ximena, additional, Cetin, Ali, additional, Smith, Kimberly A., additional, Gwinn, Ryder P., additional, Cobbs, Charles, additional, Ko, Andrew. L., additional, Ojemann, Jeffrey G., additional, Keene, C. Dirk, additional, Silbergeld, Daniel. L., additional, Sunkin, Susan M., additional, Gradinaru, Viviana, additional, Horwitz, Gregory D., additional, Zeng, Hongkui, additional, Tasic, Bosiljka, additional, Lein, Ed S., additional, Ting, Jonathan T., additional, and Levi, Boaz P., additional

Published
2019
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38. Enhancer viruses and a transgenic platform for combinatorial cell subclass-specific labeling

Author

Graybuck, Lucas T., primary, Daigle, Tanya L., additional, Sedeño-Cortés, Adriana E., additional, Walker, Miranda, additional, Kalmbach, Brian, additional, Lenz, Garreck H., additional, Nguyen, Thuc Nghi, additional, Garren, Emma, additional, Kim, Tae Kyung, additional, Siverts, La’ Akea, additional, Bendrick, Jacqueline L., additional, Zhou, Thomas, additional, Mortrud, Marty, additional, Yao, Shenqin, additional, Cetin, Ali H., additional, Larsen, Rachael, additional, Esposito, Luke, additional, Gore, Bryan, additional, Szelenyi, Eric, additional, Morin, Elyse, additional, Mich, John K., additional, Dee, Nick, additional, Goldy, Jeff, additional, Smith, Kimberly, additional, Yao, Zizhen, additional, Gradinaru, Viviana, additional, Sunkin, Susan M., additional, Lein, Ed, additional, Levi, Boaz P., additional, Ting, Jonathan T., additional, Zeng, Hongkui, additional, and Tasic, Bosiljka, additional

Published
2019
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39. Single-nucleus and single-cell transcriptomes compared in matched cortical cell types

Author

Bakken, Trygve E., primary, Hodge, Rebecca D., additional, Miller, Jeremy A., additional, Yao, Zizhen, additional, Nguyen, Thuc Nghi, additional, Aevermann, Brian, additional, Barkan, Eliza, additional, Bertagnolli, Darren, additional, Casper, Tamara, additional, Dee, Nick, additional, Garren, Emma, additional, Goldy, Jeff, additional, Graybuck, Lucas T., additional, Kroll, Matthew, additional, Lasken, Roger S., additional, Lathia, Kanan, additional, Parry, Sheana, additional, Rimorin, Christine, additional, Scheuermann, Richard H., additional, Schork, Nicholas J., additional, Shehata, Soraya I., additional, Tieu, Michael, additional, Phillips, John W., additional, Bernard, Amy, additional, Smith, Kimberly A., additional, Zeng, Hongkui, additional, Lein, Ed S., additional, and Tasic, Bosiljka, additional

Published
2018
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40. Conserved cell types with divergent features between human and mouse cortex

Author

Hodge, Rebecca D, primary, Bakken, Trygve E, additional, Miller, Jeremy A, additional, Smith, Kimberly A, additional, Barkan, Eliza R, additional, Graybuck, Lucas T, additional, Close, Jennie L, additional, Long, Brian, additional, Penn, Osnat, additional, Yao, Zizhen, additional, Eggermont, Jeroen, additional, Hollt, Thomas, additional, Levi, Boaz P, additional, Shehata, Soraya I, additional, Aevermann, Brian, additional, Beller, Allison, additional, Bertagnolli, Darren, additional, Brouner, Krissy, additional, Casper, Tamara, additional, Cobbs, Charles, additional, Dalley, Rachel, additional, Dee, Nick, additional, Ding, Song-Lin, additional, Ellenbogen, Richard G, additional, Fong, Olivia, additional, Garren, Emma, additional, Goldy, Jeff, additional, Gwinn, Ryder P, additional, Hirschstein, Daniel, additional, Keene, C Dirk, additional, Keshk, Mohamed, additional, Ko, Andrew L, additional, Lathia, Kanan, additional, Mahfouz, Ahmed, additional, Maltzer, Zoe, additional, McGraw, Medea, additional, Nguyen, Thuc Nghi, additional, Nyhus, Julie, additional, Ojemann, Jeffrey G, additional, Oldre, Aaron, additional, Parry, Sheana, additional, Reynolds, Shannon, additional, Rimorin, Christine, additional, Shapovalova, Nadiya V, additional, Somasundaram, Saroja, additional, Szafer, Aaron, additional, Thomsen, Elliot R, additional, Tieu, Michael, additional, Scheuermann, Richard H, additional, Yuste, Rafael, additional, Sunkin, Susan M, additional, Lelieveldt, Boudewijn, additional, Feng, David, additional, Ng, Lydia, additional, Bernard, Amy, additional, Hawrylycz, Michael, additional, Phillips, John W., additional, Tasic, Bosiljka, additional, Zeng, Hongkui, additional, Jones, Allan R, additional, Koch, Christof, additional, and Lein, Ed S, additional

Published
2018
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41. A Suite of Transgenic Driver and Reporter Mouse Lines with Enhanced Brain-Cell-Type Targeting and Functionality

Author

Daigle, Tanya L., primary, Madisen, Linda, additional, Hage, Travis A., additional, Valley, Matthew T., additional, Knoblich, Ulf, additional, Larsen, Rylan S., additional, Takeno, Marc M., additional, Huang, Lawrence, additional, Gu, Hong, additional, Larsen, Rachael, additional, Mills, Maya, additional, Bosma-Moody, Alice, additional, Siverts, La’ Akea, additional, Walker, Miranda, additional, Graybuck, Lucas T., additional, Yao, Zizhen, additional, Fong, Olivia, additional, Nguyen, Thuc Nghi, additional, Garren, Emma, additional, Lenz, Garreck H., additional, Chavarha, Mariya, additional, Pendergraft, Julie, additional, Harrington, James, additional, Hirokawa, Karla E., additional, Harris, Julie A., additional, Nicovich, Philip R., additional, McGraw, Medea J., additional, Ollerenshaw, Douglas R., additional, Smith, Kimberly A., additional, Baker, Christopher A., additional, Ting, Jonathan T., additional, Sunkin, Susan M., additional, Lecoq, Jérôme, additional, Lin, Michael Z., additional, Boyden, Edward S., additional, Murphy, Gabe J., additional, da Costa, Nuno M., additional, Waters, Jack, additional, Li, Lu, additional, Tasic, Bosiljka, additional, and Zeng, Hongkui, additional

Published
2018
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42. Distinct descending motor cortex pathways and their roles in movement

Author

Economo, Michael N., primary, Viswanathan, Sarada, additional, Tasic, Bosiljka, additional, Bas, Erhan, additional, Winnubst, Johan, additional, Menon, Vilas, additional, Graybuck, Lucas T., additional, Nguyen, Thuc Nghi, additional, Wang, Lihua, additional, Gerfen, Charles R., additional, Chandrashekar, Jayaram, additional, Zeng, Hongkui, additional, Looger, Loren L., additional, and Svoboda, Karel, additional

Published
2017
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43. A suite of transgenic driver and reporter mouse lines with enhanced brain cell type targeting and functionality

Author

Daigle, Tanya L., primary, Madisen, Linda, additional, Hage, Travis A., additional, Valley, Matthew T., additional, Knoblich, Ulf, additional, Larsen, Rylan S., additional, Takeno, Marc M., additional, Huang, Lawrence, additional, Gu, Hong, additional, Larsen, Rachael, additional, Mills, Maya, additional, Bosma-Moody, Alice, additional, Siverts, La’Akea, additional, Walker, Miranda, additional, Graybuck, Lucas T., additional, Yao, Zizhen, additional, Fong, Olivia, additional, Garren, Emma, additional, Lenz, Garreck, additional, Chavarha, Mariya, additional, Pendergraft, Julie, additional, Harrington, James, additional, Hirokawa, Karla E., additional, Harris, Julie A., additional, McGraw, Medea, additional, Ollerenshaw, Douglas R., additional, Smith, Kimberly, additional, Baker, Christopher A., additional, Ting, Jonathan T., additional, Sunkin, Susan M., additional, Lecoq, Jerome, additional, Lin, Michael Z., additional, Boyden, Edward S., additional, Murphy, Gabe J., additional, da Costa, Nuno, additional, Waters, Jack, additional, Li, Lu, additional, Tasic, Bosiljka, additional, and Zeng, Hongkui, additional

Published
2017
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44. Author Correction: Trimodal single-cell profiling reveals a novel pediatric CD8αα+T cell subset and broad age-related molecular reprogramming across the T cell compartment

Author

Thomson, Zachary, He, Ziyuan, Swanson, Elliott, Henderson, Katherine, Phalen, Cole, Zaim, Samir Rachid, Pebworth, Mark-Phillip, Okada, Lauren Y., Heubeck, Alexander T., Roll, Charles R., Hernandez, Veronica, Weiss, Morgan, Genge, Palak C., Reading, Julian, Giles, Josephine R., Manne, Sasikanth, Dougherty, Jeanette, Jasen, C. J., Greenplate, Allison R., Becker, Lynne A., Graybuck, Lucas T., Vasaikar, Suhas V., Szeto, Gregory L., Savage, Adam K., Speake, Cate, Buckner, Jane H., Li, Xiao-jun, Bumol, Thomas F., Wherry, E.John, Torgerson, Troy R., Vella, Laura A., Henrickson, Sarah E., Skene, Peter J., and Gustafson, Claire E.

Published
2024
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45. Longitudinal Multi-omic Immune Profiling Reveals Age-Related Immune Cell Dynamics in Healthy Adults.

Author

Gong Q, Sharma M, Kuan EL, Glass MC, Chander A, Singh M, Graybuck LT, Thomson ZJ, LaFrance CM, Zaim SR, Peng T, Okada LY, Genge PC, Henderson KE, Dornisch EM, Layton ED, Wittig PJ, Heubeck AT, Mukuka NM, Reading J, Roll CR, Hernandez V, Parthasarathy V, Stuckey TJ, Musgrove B, Swanson E, Lord C, Weiss MDA, Phalen CG, Mettey RR, Lee KJ, Johanneson JB, Kawelo EK, Garber J, Krishnan U, Smithmyer M, Wherry EJ, Vella L, Henrickson SE, Kopp MS, Savage AK, Becker LA, Meijer P, Coffey EM, Goronzy JJ, Speake C, Bumol TF, Goldrath AW, Torgerson TR, Li XJ, Skene PJ, Buckner JH, and Gustafson CE

Abstract

The generation and maintenance of protective immunity is a dynamic interplay between host and environment that is impacted by age. Understanding fundamental changes in the healthy immune system that occur over a lifespan is critical in developing interventions for age-related susceptibility to infections and diseases. Here, we use multi-omic profiling (scRNA-seq, proteomics, flow cytometry) to examined human peripheral immunity in over 300 healthy adults, with 96 young and older adults followed over two years with yearly vaccination. The resulting resource includes scRNA-seq datasets of >16 million PBMCs, interrogating 71 immune cell subsets from our new Immune Health Atlas. This study allows unique insights into the composition and transcriptional state of immune cells at homeostasis, with vaccine perturbation, and across age. We find that T cells specifically accumulate age-related transcriptional changes more than other immune cells, independent from inflammation and chronic perturbation. Moreover, impaired memory B cell responses to vaccination are linked to a Th2-like state shift in older adults' memory CD4 T cells, revealing possible mechanisms of immune dysregulation during healthy human aging. This extensive resource is provided with a suite of exploration tools at https://apps.allenimmunology.org/aifi/insights/dynamics-imm-health-age/ to enhance data accessibility and further the understanding of immune health across age., Competing Interests: Conflicts of Interest. A.W.G. serves on the scientific advisory boards of ArsenalBio and Foundery Innovations and is a cofounder of TCura. All other authors declare no conflict of interest.

Published
2024
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46. Longitudinal immune dynamics of mild COVID-19 define signatures of recovery and persistence.

Author

Talla A, Vasaikar SV, Lemos MP, Moodie Z, Lee Pebworth MP, Henderson KE, Cohen KW, Czartoski JL, Lai L, Suthar MS, Heubeck AT, Genge PC, Roll CR, Weiss M, Reading J, Kondza N, MacMillan H, Fong OC, Thomson ZJ, Graybuck LT, Okada LY, Newell EW, Coffey EM, Meijer P, Becker LA, De Rosa SC, Skene PJ, Torgerson TR, Li XJ, Szeto GL, McElrath MJ, and Bumol TF

Abstract

SARS-CoV-2 has infected over 200 million and caused more than 4 million deaths to date. Most individuals (>80%) have mild symptoms and recover in the outpatient setting, but detailed studies of immune responses have focused primarily on moderate to severe COVID-19. We deeply profiled the longitudinal immune response in individuals with mild COVID-19 beginning with early time points post-infection (1-15 days) and proceeding through convalescence to >100 days after symptom onset. We correlated data from single cell analyses of peripheral blood cells, serum proteomics, virus-specific cellular and humoral immune responses, and clinical metadata. Acute infection was characterized by vigorous coordinated innate and adaptive immune activation that differed in character by age (young vs. old). We then characterized signals associated with recovery and convalescence to define and validate a new signature of inflammatory cytokines, gene expression, and chromatin accessibility that persists in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC).

Published
2021
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