A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex

Yao, Zizhen; Liu, Hanqing; Xie, Fangming; Fischer, Stephan; Adkins, Ricky S.; Aldridge, Andrew I.; Ament, Seth A.; Bartlett, Anna; Behrens, M. Margarita; Berge, Koen; Bertagnolli, Darren; Bézieux, Hector Roux; Biancalani, Tommaso; Booeshaghi, A. Sina; Bravo, Héctor Corrada; Casper, Tamara; Colantuoni, Carlo; Crabtree, Jonathan; Creasy, Heather; Crichton, Kirsten; Crow, Megan; Dee, Nick; Dougherty, Elizabeth L.; Doyle, Wayne I.; Dudoit, Sandrine; Fang, Rongxin; Felix, Victor; Fong, Olivia; Giglio, Michelle; Goldy, Jeff; Hawrylycz, Mike; Herb, Brian R.; Hertzano, Ronna; Hou, Xiaomeng; Hu, Qiwen; Kancherla, Jayaram; Kroll, Matthew; Lathia, Kanan; Li, Yang Eric; Lucero, Jacinta D.; Luo, Chongyuan; Mahurkar, Anup; McMillen, Delissa; Nadaf, Naeem M.; Nery, Joseph R.; Nguyen, Thuc Nghi; Niu, Sheng-Yong; Ntranos, Vasilis; Orvis, Joshua; Osteen, Julia K.; Pham, Thanh; Pinto-Duarte, Antonio; Poirion, Olivier; Preissl, Sebastian; Purdom, Elizabeth; Rimorin, Christine; Risso, Davide; Rivkin, Angeline C.; Smith, Kimberly; Street, Kelly; Sulc, Josef; Svensson, Valentine; Tieu, Michael; Torkelson, Amy; Tung, Herman; Vaishnav, Eeshit Dhaval; Vanderburg, Charles R.; Velthoven, Cindy; Wang, Xinxin; White, Owen R.; Huang, Z. Josh; Kharchenko, Peter V.; Pachter, Lior; Ngai, John; Regev, Aviv; Tasic, Bosiljka; Welch, Joshua D.; Gillis, Jesse; Macosko, Evan Z.; Ren, Bing; Ecker, Joseph R.; Zeng, Hongkui; Mukamel, Eran A.

A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex

Zizhen Yao, Hanqing Liu, Fangming Xie, Stephan Fischer, Ricky S. Adkins, Andrew I. Aldridge, Seth A. Ament, Anna Bartlett, M. Margarita Behrens, Koen Berge, Darren Bertagnolli, Hector Roux Bézieux, Tommaso Biancalani, A. Sina Booeshaghi, Héctor Corrada Bravo, Tamara Casper, Carlo Colantuoni, Jonathan Crabtree, Heather Creasy, Kirsten Crichton, Megan Crow, Nick Dee, Elizabeth L. Dougherty, Wayne I. Doyle, Sandrine Dudoit, Rongxin Fang, Victor Felix, Olivia Fong, Michelle Giglio, Jeff Goldy, Mike Hawrylycz, Brian R. Herb, Ronna Hertzano, Xiaomeng Hou, Qiwen Hu, Jayaram Kancherla, Matthew Kroll, Kanan Lathia, Yang Eric Li, Jacinta D. Lucero, Chongyuan Luo, Anup Mahurkar, Delissa McMillen, Naeem M. Nadaf, Joseph R. Nery, Thuc Nghi Nguyen, Sheng-Yong Niu, Vasilis Ntranos, Joshua Orvis, Julia K. Osteen, Thanh Pham, Antonio Pinto-Duarte, Olivier Poirion, Sebastian Preissl, Elizabeth Purdom, Christine Rimorin, Davide Risso, Angeline C. Rivkin, Kimberly Smith, Kelly Street, Josef Sulc, Valentine Svensson, Michael Tieu, Amy Torkelson, Herman Tung, Eeshit Dhaval Vaishnav, Charles R. Vanderburg, Cindy Velthoven, Xinxin Wang, Owen R. White, Z. Josh Huang, Peter V. Kharchenko, Lior Pachter, John Ngai, Aviv Regev, Bosiljka Tasic, Joshua D. Welch, Jesse Gillis, Evan Z. Macosko, Bing Ren, Joseph R. Ecker, Hongkui Zeng () and Eran A. Mukamel ()
Additional contact information
Zizhen Yao: Allen Institute for Brain Science
Hanqing Liu: The Salk Institute for Biological Studies
Fangming Xie: University of California, San Diego
Stephan Fischer: Cold Spring Harbor Laboratory
Ricky S. Adkins: University of Maryland School of Medicine
Andrew I. Aldridge: The Salk Institute for Biological Studies
Seth A. Ament: University of Maryland School of Medicine
Anna Bartlett: The Salk Institute for Biological Studies
M. Margarita Behrens: The Salk Institute for Biological Studies
Koen Berge: University of California, Berkeley
Darren Bertagnolli: Allen Institute for Brain Science
Hector Roux Bézieux: School of Public Health, University of California, Berkeley
Tommaso Biancalani: Broad Institute of MIT and Harvard
A. Sina Booeshaghi: California Institute of Technology
Héctor Corrada Bravo: University of Maryland, College Park
Tamara Casper: Allen Institute for Brain Science
Carlo Colantuoni: Johns Hopkins School of Medicine, Department of Neurology
Jonathan Crabtree: University of Maryland School of Medicine
Heather Creasy: University of Maryland School of Medicine
Kirsten Crichton: Allen Institute for Brain Science
Megan Crow: Cold Spring Harbor Laboratory
Nick Dee: Allen Institute for Brain Science
Elizabeth L. Dougherty: Broad Institute of MIT and Harvard
Wayne I. Doyle: University of California, San Diego
Sandrine Dudoit: University of California, Berkeley
Rongxin Fang: University of California, San Diego
Victor Felix: University of Maryland School of Medicine
Olivia Fong: Allen Institute for Brain Science
Michelle Giglio: University of Maryland School of Medicine
Jeff Goldy: Allen Institute for Brain Science
Mike Hawrylycz: Allen Institute for Brain Science
Brian R. Herb: University of Maryland School of Medicine
Ronna Hertzano: University of Maryland School of Medicine
Xiaomeng Hou: University of California, San Diego School of Medicine
Qiwen Hu: Harvard Medical School
Jayaram Kancherla: University of Maryland, College Park
Matthew Kroll: Allen Institute for Brain Science
Kanan Lathia: Allen Institute for Brain Science
Yang Eric Li: Ludwig Institute for Cancer Research
Jacinta D. Lucero: The Salk Institute for Biological Studies
Chongyuan Luo: The Salk Institute for Biological Studies
Anup Mahurkar: University of Maryland School of Medicine
Delissa McMillen: Allen Institute for Brain Science
Naeem M. Nadaf: Broad Institute of MIT and Harvard
Joseph R. Nery: The Salk Institute for Biological Studies
Thuc Nghi Nguyen: Allen Institute for Brain Science
Sheng-Yong Niu: The Salk Institute for Biological Studies
Vasilis Ntranos: University of California, San Francisco
Joshua Orvis: University of Maryland School of Medicine
Julia K. Osteen: The Salk Institute for Biological Studies
Thanh Pham: Allen Institute for Brain Science
Antonio Pinto-Duarte: The Salk Institute for Biological Studies
Olivier Poirion: University of California, San Diego School of Medicine
Sebastian Preissl: University of California, San Diego School of Medicine
Elizabeth Purdom: University of California, Berkeley
Christine Rimorin: Allen Institute for Brain Science
Davide Risso: University of Padova
Angeline C. Rivkin: The Salk Institute for Biological Studies
Kimberly Smith: Allen Institute for Brain Science
Kelly Street: Dana-Farber Cancer Institute
Josef Sulc: Allen Institute for Brain Science
Valentine Svensson: California Institute of Technology
Michael Tieu: Allen Institute for Brain Science
Amy Torkelson: Allen Institute for Brain Science
Herman Tung: Allen Institute for Brain Science
Eeshit Dhaval Vaishnav: Broad Institute of MIT and Harvard
Charles R. Vanderburg: Broad Institute of MIT and Harvard
Cindy Velthoven: Allen Institute for Brain Science
Xinxin Wang: University of California, San Diego School of Medicine
Owen R. White: University of Maryland School of Medicine
Z. Josh Huang: Cold Spring Harbor Laboratory
Peter V. Kharchenko: Harvard Medical School
Lior Pachter: California Institute of Technology
John Ngai: University of California, Berkeley
Aviv Regev: Broad Institute of MIT and Harvard
Bosiljka Tasic: Allen Institute for Brain Science
Joshua D. Welch: University of Michigan
Jesse Gillis: Cold Spring Harbor Laboratory
Evan Z. Macosko: Broad Institute of MIT and Harvard
Bing Ren: University of California, San Diego School of Medicine
Joseph R. Ecker: The Salk Institute for Biological Studies
Hongkui Zeng: Allen Institute for Brain Science
Eran A. Mukamel: University of California, San Diego

Nature, 2021, vol. 598, issue 7879, 103-110

Abstract: Abstract Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain1–3. With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the mouse primary motor cortex, a structure that has an evolutionarily conserved role in locomotion. We developed computational and statistical methods to integrate multimodal data and quantitatively validate cell-type reproducibility. The resulting reference atlas—containing over 56 neuronal cell types that are highly replicable across analysis methods, sequencing technologies and modalities—is a comprehensive molecular and genomic account of the diverse neuronal and non-neuronal cell types in the mouse primary motor cortex. The atlas includes a population of excitatory neurons that resemble pyramidal cells in layer 4 in other cortical regions4. We further discovered thousands of concordant marker genes and gene regulatory elements for these cell types. Our results highlight the complex molecular regulation of cell types in the brain and will directly enable the design of reagents to target specific cell types in the mouse primary motor cortex for functional analysis.

Date: 2021
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DOI: 10.1038/s41586-021-03500-8

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