Comparative cellular analysis of motor cortex in human, marmoset and mouse
Authors: 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. 
Published: October 2021

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.