A transcriptomic and epigenomic cell atlas of the mouse primary motor cortex
Zizhen Yao, Hanqing Liu, Fangming Xie, Stephan Fischer, Ricky S. Adkins, Andrew Aldridge, Seth A. Ament, Anna Bartlett, M. Margarita Behrens, Koen Van Den Berge, Darren Bertagnolli, Hector Roux de Bézieux, Tommaso Biancalani, A. Sina Booeshaghi, Héctor Corrada Bravo, Tamara Casper, Carlo Colantuoni, Jonathan Crabtree, Heather H. 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 Lucero, Chongyuan Luo, Anup Mahurkar, Delissa McMillen, Naeem Nadaf, Joseph R. Nery, Thuc Nghi Nguyen, Sheng-Yong Niu, Vasilis Ntranos, Joshua Orvis, Julia Osteen, Thanh Pham, António Pinto‐Duarte, Olivier Poirion, Sebastian Preißl, Elizabeth Purdom, Christine Rimorin, Davide Risso, Angeline Rivkin, Kimberly A. Smith, Kelly Street, Josef Šulc, Valentine Svensson, Michael Tieu, Amy Torkelson, Herman Tung, Eeshit Dhaval Vaishnav, Charles Vanderburg, Cindy T. J. van Velthoven, Xinxin Wang, Owen 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, Eran A. Mukamel
Abstract
Abstract Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain 1–3 . 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 regions 4 . 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.