PT  - JOURNAL ARTICLE
AU  - Trygve E. Bakken
AU  - Nikolas L. Jorstad
AU  - Qiwen Hu
AU  - Blue B. Lake
AU  - Wei Tian
AU  - Brian E. Kalmbach
AU  - Megan Crow
AU  - Rebecca D. Hodge
AU  - Fenna M. Krienen
AU  - Staci A. Sorensen
AU  - Jeroen Eggermont
AU  - Zizhen Yao
AU  - Brian D. Aevermann
AU  - Andrew I. Aldridge
AU  - Anna Bartlett
AU  - Darren Bertagnolli
AU  - Tamara Casper
AU  - Rosa G. Castanon
AU  - Kirsten Crichton
AU  - Tanya L. Daigle
AU  - Rachel Dalley
AU  - Nick Dee
AU  - Nikolai Dembrow
AU  - Dinh Diep
AU  - Song-Lin Ding
AU  - Weixiu Dong
AU  - Rongxin Fang
AU  - Stephan Fischer
AU  - Melissa Goldman
AU  - Jeff Goldy
AU  - Lucas T. Graybuck
AU  - Brian R. Herb
AU  - Xiaomeng Hou
AU  - Jayaram Kancherla
AU  - Matthew Kroll
AU  - Kanan Lathia
AU  - Baldur van Lew
AU  - Yang Eric Li
AU  - Christine S. Liu
AU  - Hanqing Liu
AU  - Anup Mahurkar
AU  - Delissa McMillen
AU  - Jeremy A. Miller
AU  - Marmar Moussa
AU  - Joseph R. Nery
AU  - Joshua Orvis
AU  - Scott Owen
AU  - Carter R. Palmer
AU  - Thanh Pham
AU  - Nongluk Plongthongkum
AU  - Olivier Poirion
AU  - Nora M. Reed
AU  - Christine Rimorin
AU  - Angeline Rivkin
AU  - William J. Romanow
AU  - Adriana E. Sedeño-Cortés
AU  - Kimberly Siletti
AU  - Saroja Somasundaram
AU  - Josef Sulc
AU  - Michael Tieu
AU  - Amy Torkelson
AU  - Herman Tung
AU  - Xinxin Wang
AU  - Fangming Xie
AU  - Anna Marie Yanny
AU  - Renee Zhang
AU  - Seth A. Ament
AU  - Hector Corrada Bravo
AU  - Jerold Chun
AU  - Alexander Dobin
AU  - Jesse Gillis
AU  - Ronna Hertzano
AU  - Patrick R. Hof
AU  - Thomas Höllt
AU  - Gregory D. Horwitz
AU  - C. Dirk Keene
AU  - Peter V. Kharchenko
AU  - Andrew L. Ko
AU  - Boudewijn P. Lelieveldt
AU  - Chongyuan Luo
AU  - Eran A. Mukamel
AU  - Sebastian Preissl
AU  - Aviv Regev
AU  - Bing Ren
AU  - Richard H. Scheuermann
AU  - Kimberly Smith
AU  - William J. Spain
AU  - Owen R. White
AU  - Christof Koch
AU  - Michael Hawrylycz
AU  - Bosiljka Tasic
AU  - Evan Z. Macosko
AU  - Steven A. McCarroll
AU  - Jonathan T. Ting
AU  - Hongkui Zeng
AU  - Kun Zhang
AU  - Guoping Feng
AU  - Joseph R. Ecker
AU  - Sten Linnarsson
AU  - Ed S. Lein
TI  - Evolution of cellular diversity in primary motor cortex of human, marmoset monkey, and mouse
AID  - 10.1101/2020.03.31.016972
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.31.016972
4099  - http://biorxiv.org/content/early/2020/04/01/2020.03.31.016972.short
4100  - http://biorxiv.org/content/early/2020/04/01/2020.03.31.016972.full
AB  - 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.