A multimodal cell census and atlas of the mammalian primary motor cortex
Authors:   BRAIN Initiative Cell Census Network (BICCN), Adkins Ricky S. , Aldridge Andrew I. , Allen Shona , Ament Seth A. , An Xu , Armand Ethan , Ascoli Giorgio A. , Bakken Trygve E. , Bandrowski Anita , Banerjee Samik , Barkas Nikolaos , Bartlett Anna , Bateup Helen S. , Behrens M. Margarita , Berens Philipp , Berg Jim , Bernabucci Matteo , Bernaerts Yves , Bertagnolli Darren , Biancalani Tommaso , Boggeman Lara , Booeshaghi A. Sina , Bowman Ian , Bravo Héctor Corrada , Cadwell Cathryn René , Callaway Edward M. , Carlin Benjamin , O'Connor Carolyn , Carter Robert , Casper Tamara , Castanon Rosa G. , Castro Jesus Ramon , Chance Rebecca K. , Chatterjee Apaala , Chen Huaming , Chun Jerold , Colantuoni Carlo , Crabtree Jonathan , Creasy Heather , Crichton Kirsten , Crow Megan , D'Orazi Florence D. , Daigle Tanya L. , Dalley Rachel , Dee Nick , Degatano Kylee , Dichter Benjamin , Diep Dinh , Ding Liya , Ding Song-Lin , Dominguez Bertha , Dong Hong-Wei , Dong Weixiu , Dougherty Elizabeth L. , Dudoit Sandrine , Ecker Joseph R. , Eichhorn Stephen W. , Fang Rongxin , Felix Victor , Feng Guoping , Feng Zhao , Fischer Stephan , Fitzpatrick Conor , Fong Olivia , Foster Nicholas N. , Galbavy William , Gee James C. , Ghosh Satrajit S. , Giglio Michelle , Gillespie Thomas H. , Gillis Jesse , Goldman Melissa , Goldy Jeff , Gong Hui , Gou Lin , Grauer Michael , Halchenko Yaroslav O. , Harris Julie A. , Hartmanis Leonard , Hatfield Joshua T. , Hawrylycz Mike , Helba Brian , Herb Brian R. , Hertzano Ronna , Hintiryan Houri , Hirokawa Karla E. , Hockemeyer Dirk , Hodge Rebecca D. , Hood Greg , Horwitz Gregory D. , Hou Xiaomeng , Hu Lijuan , Hu Qiwen , Huang Z. Josh , Huo Bingxing , Ito-Cole Tony , Jacobs Matthew , Jia Xueyan , Jiang Shengdian , Jiang Tao , Jiang Xiaolong , Jin Xin , Jorstad Nikolas L. , Kalmbach Brian E. , Kancherla Jayaram , Keene C. Dirk , Kelly Kathleen , Khajouei Farzaneh , Kharchenko Peter V. , Kim Gukhan , Ko Andrew L. , Kobak Dmitry , Konwar Kishori , Kramer Daniel J. , Krienen Fenna M. , Kroll Matthew , Kuang Xiuli , Kuo Hsien-Chi , Lake Blue B. , Larsen Rachael , Lathia Kanan , Laturnus Sophie , Lee Angus Y. , Lee Cheng-Ta , Lee Kuo-Fen , Lein Ed S. , Lesnar Phil , Li Anan , Li Xiangning , Li Xu , Li Yang Eric , Li Yaoyao , Li Yuanyuan , Lim Byungkook , Linnarsson Sten , Liu Christine S. , Liu Hanqing , Liu Lijuan , Lucero Jacinta D. , Luo Chongyuan , Luo Qingming , Macosko Evan Z. , Mahurkar Anup , Martone Maryann E. , Matho Katherine S. , McCarroll Steven A. , McCracken Carrie , McMillen Delissa , Miranda Elanine , Mitra Partha P , Miyazaki Paula Assakura , Mizrachi Judith , Mok Stephanie , Mukamel Eran A. , Mulherkar Shalaka , Nadaf Naeem M. , Naeemi Maitham , Narasimhan Arun , Nery Joseph R. , Ng Lydia , Ngai John , Nguyen Thuc Nghi , Nickel Lance , Nicovich Philip R. , Niu Sheng-Yong , Ntranos Vasilis , Nunn Michael , Olley Dustin , Orvis Joshua , Osteen Julia K. , Osten Pavel , Owen Scott F. , Pachter Lior , Palaniswamy Ramesh , Palmer Carter R. , Pang Yan , Peng Hanchuan , Pham Thanh , Pinto-Duarte Antonio , Plongthongkum Nongluk , Poirion Olivier , Preissl Sebastian , Purdom Elizabeth , Qu Lei , Rashid Mohammad , Reed Nora M. , Regev Aviv , Ren Bing , Ren Miao , Rimorin Christine , Risso Davide , Rivkin Angeline C. , Muñoz-Castañeda Rodrigo , Romanow William J. , Ropelewski Alexander J. , Roux de Bézieux Hector , Ruan Zongcai , Sandberg Rickard , Savoia Steven , Scala Federico , Schor Michael , Shen Elise , Siletti Kimberly , Smith Jared B. , Smith Kimberly , Somasundaram Saroja , Song Yuanyuan , Sorensen Staci A. , Stafford David A. , Street Kelly , Sulc Josef , Sunkin Susan , Svensson Valentine , Tan Pengcheng , Tan Zheng Huan , Tasic Bosiljka , Thompson Carol , Tian Wei , Tickle Timothy L. , Tieu Michael , Ting Jonathan T. , Tolias Andreas Savas , Torkelson Amy , Tung Herman , Vaishnav Eeshit Dhaval , Van den Berge Koen , van Velthoven Cindy T.J. , Vanderburg Charles R. , Veldman Matthew B. , Vu Minh , Wakeman Wayne , Wang Peng , Wang Quanxin , Wang Xinxin , Wang Yimin , Wang Yun , Welch Joshua D. , White Owen , Williams Elora , Xie Fangming , Xie Peng , Xiong Feng , Yang X. William , Yanny Anna Marie , Yao Zizhen , Yin Lulu , Yu Yang , Yuan Jing , Zeng Hongkui , Zhang Kun , Zhang Meng , Zhang Zhuzhu , Zhao Sujun , Zhao Xuan , Zhou Jingtian , Zhuang Xiaowei , Zingg Brian 
Published: October 2020

ABSTRACTWe report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth,in situsingle-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.