A multimodal cell census and atlas of the mammalian primary motor cortex

作者：BRAIN Initiative Cell Census Network (BICCN), BRAIN Initiative Cell Census Network (BICCN) Corresponding authors, Edward M. Callaway, Hong‐Wei Dong, Joseph R. Ecker, Michael Hawrylycz, Z. Josh Huang, Ed S. Lein, John Ngai, Pavel Osten, Bing Ren, Andreas Savas Tolias, Owen R. White, Hongkui Zeng, Xiaowei Zhuang, BICCN contributing principal investigators, Giorgio A. Ascoli, M. Margarita Behrens, Jerold J. M. Chun, Guoping Feng, James C. Gee, Satrajit Ghosh, Yaroslav O. Halchenko, Ronna P. Hertzano, Byung Kook Lim, Maryann Elizabeth Martone, Lydia Ng, Lior S. Pachter, Alexander J. Ropelewski, Timothy L. Tickle, X. William Yang, Kun Zhang, Principal manuscript editors, Manuscript writing and figure generation, Trygve E. Bakken, Philipp Berens, Tanya L. Daigle, Julie A. Harris, Nikolas L. Jorstad, Brian E. Kalmbach, Dmitry Kobak, Yang Eric Li, Hanqing Liu, Katherine S. Matho, Eran A. Mukamel, Maitham Naeemi, Federico Scala, Pengcheng Tan, Jonathan T. Ting, Fangming Xie, Meng Zhang, Zhuzhu Zhang, Jingtian Zhou, Brian Zingg, Analysis coordination, Integrated data analysis, Ethan J. Armand, Zizhen Yao, scRNA-seq and snRNA-seq data generation and processing, Darren Bertagnolli, Tamara Casper, Kirsten Crichton, Nick Dee, Dinh Diep, Song‐Lin Ding, Weixiu Dong, Elizabeth L. Dougherty, Olivia Fong, Melissa Goldman, Jeff Goldy, Rebecca D. Hodge, Lijuan Hu, Christopher Dirk Keene, Fenna M. Krienen, Matthew R Kroll, Blue B. Lake, Kanan B. Lathia, Sten Linnarsson, Christine S. Liu, Evan Z. Macosko, Steven A. McCarroll, Delissa McMillen, Naeem M. Nadaf, Thuc Nghi Nguyen, Carter R. Palmer, Thanh Thi Mai Pham, Nongluk Plongthongkum, Nora M. Reed, Aviv Regev, Christine Rimorin, William J. Romanow, Stephen Savoia, Kimberly Siletti, Kimberly A. Smith, Josef Šulc, Bosiljka Tasic, Michael Tieu, Amy Torkelson, Herman Tung, Cindy T. J. van Velthoven, Charles R. Vanderburg, Anna Marie Yanny, ATAC-seq data generation and processing, Rongxin Fang, Xiaomeng Hou, Jacinta D. Lucero, Julia K. Osteen, António Pinto‐Duarte, Olivier Poirion, Sebastian Preißl, Xinxin Wang, Methylcytosine data production and analysis, Andrew I. Aldridge, Anna Bartlett, Lara Boggeman, Carolyn O’Connor, Rosa Castanon, Huaming Chen, Conor Fitzpatrick, Chongyuan Luo, Joseph R. Nery, Michael F. Nunn, Angeline C. Rivkin, Wei Tian, Epi-retro-seq data generation and processing, Bertha Dominguez, Tony Ito-Cole, Matthew W. Jacobs, Xin Jin, Cheng-Ta Lee, Kuo‐Fen Lee, Paula Assakura Miyazaki, Yan Pang, Mohammad Rashid, Jared B. Smith, Minh Vu, Elora Williams, ‘Omics data analysis, Tommaso Biancalani, A. Sina Booeshaghi, Megan Crow, Sandrine Dudoit, Stephan Fischer, Jesse A Gillis, Qiwen Hu, Peter V. Kharchenko, Sheng-Yong Niu, Vasilis Ntranos, Elizabeth Purdom, Davide Risso, Hector Roux de Bézieux, Saroja Somasundaram, Kelly Street, Valentine Svensson, Eeshit Dhaval Vaishnav, Koen Van Den Berge, Joshua D. Welch, Tracing and connectivity data generation, Xu An, Helen S. Bateup, Ian Bowman, Rebecca K. Chance, Nicholas N. Foster, William Galbavy, Hui Gong, Lin Gou, Joshua T. Hatfield, Houri Hintiryan, Karla E. Hirokawa, Gukhan Kim, Daniel J. Kramer, Anan Li, Xiangning Li, Qingming Luo, Rodrigo Muñoz-Castañeda, David A. Stafford, Morphology data generation and reconstruction, Zhao Feng, Xueyan Jia, Shengdian Jiang, Tao Jiang, Xiuli Kuang, Rachael Larsen, Phil Lesnar, Yaoyao Li, Yuanyuan Li, Lijuan Liu, Hanchuan Peng, Lei Qu, Miao Ren, Zongcai Ruan, Elise Shen, Yuanyuan Song, Wayne Wakeman, Peng Wang, Yimin Wang, Yun Wang, Lulu Yin, Jing Yuan, Sujun Zhao, Xuan Zhao, OLST/STPT and other data generation, Arun Narasimhan, Ramesh Palaniswamy, Morphology, connectivity and imaging analysis, Samik Banerjee, Liya Ding, Dhananjay Huilgol, Bing‐Xing Huo, Hsien-Chi Kuo, Sophie Laturnus, Xu Li, Partha P. Mitra, Judith Mizrachi, Quanxin Wang, Peng Xie, Feng Xiong, Yang Yu, Spatially resolved single-cell transcriptomics (MERFISH), Stephen W. Eichhorn, Multimodal profiling (Patch-seq), Jim Berg, Matteo Bernabucci, Yves Bernaerts, Cathryn René Cadwell, Jesus Ramon Castro, Rachel A. Dalley, Leonard Hartmanis, Gregory D. Horwitz, Xiaolong Jiang, Andrew Lin Ko, Elanine Miranda, Shalaka A. Mulherkar, Philip R. Nicovich, Scott F. Owen, Rickard Sandberg, Staci A. Sorensen, Zheng Huan Tan, Transgenic tools, Shona W. Allen, Dirk F. Hockemeyer, Angus Y. Lee, Matthew B. Veldman, NeMO archive and analytics, Ricky S. Adkins, Seth A. Ament, Héctor Corrada Bravo, ROBERT L. CARTER, Apaala Chatterjee, Carlo Colantuoni, Jonathan Crabtree, Heather Huot Creasy, Victor Felix, Michelle Gwinn Giglio, Brian R. Herb, Jayaram Kancherla, Anup Mahurkar, Carrie L McCracken, Lance Nickel, Dustin Olley, Joshua Orvis, Michael A Schor, Greg Hood, DANDI archive, Ben Dichter, Michael Grauer, Brian Helba, Anita E. Bandrowski, Nikolaos Barkas, Benjamin Carlin, Florence D. D’Orazi, Kylee Degatano, Tom Gillespie, Farzaneh Khajouei, Kishori M. Konwar, Carol Lynn Thompson, Project management, Kathleen Kelly, Stephanie I. Mok, Susan M. Sunkin · 发表于：Nature · 年份：2021 · DOI：10.1038/s41586-021-03950-0 · 被引用次数：588 · 研究领域：Single-cell and spatial transcriptomics、Cell Image Analysis Techniques、Neural dynamics and brain function

Abstract Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex 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. Our results advance the collective knowledge and understanding of brain cell-type organization 1–5 . First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their cir...