Evolution of cellular diversity in primary motor cortex of human, marmoset monkey, 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. , 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. , 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: April 2020

The primary motor cortex (M1) is essential for voluntary fine motor control and is functionally conserved across mammals. Using high-throughput transcriptomic and epigenomic profiling of over 450,000 single nuclei in human, marmoset monkey, and mouse, we demonstrate a broadly conserved cellular makeup of this region, whose similarity mirrors evolutionary distance and is consistent between the transcriptome and epigenome. The core conserved molecular identity of neuronal and non-neuronal types allowed the generation of a cross-species consensus cell type classification and inference of conserved cell type properties across species. Despite overall conservation, many species specializations were apparent, including differences in cell type proportions, gene expression, DNA methylation, and chromatin state. Few cell type marker genes were conserved across species, providing a short list of candidate genes and regulatory mechanisms responsible for conserved features of homologous cell types, such as the GABAergic chandelier cells. This consensus transcriptomic classification allowed the Patch-seq identification of layer 5 (L5) corticospinal Betz cells in non-human primate and human and characterization of 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.