Comparative cellular analysis of motor cortex in human, marmoset and mouse

Trygve E. Bakken, Nikolas L. Jorstad, Qiwen Hu, Blue B. Lake, Wei Tian, Brian E. Kalmbach, Megan Crow, Rebecca D. Hodge, Fenna M. Krienen, Staci A. Sorensen, Jeroen Eggermont, Zizhen Yao, Brian D. Aevermann, Andrew I. Aldridge, Anna Bartlett, Darren Bertagnolli, Tamara Casper, Rosa G. Castanon, Kirsten Crichton, Tanya L. DaigleRachel Dalley, Nick Dee, Nikolai Dembrow, Dinh Diep, Song Lin Ding, Weixiu Dong, Rongxin Fang, Stephan Fischer, Melissa Goldman, Jeff Goldy, Lucas T. Graybuck, Brian R. Herb, Xiaomeng Hou, Jayaram Kancherla, Matthew Kroll, Kanan Lathia, Baldur van Lew, Yang Eric Li, Christine S. Liu, Hanqing Liu, Jacinta D. Lucero, Anup Mahurkar, Delissa McMillen, Jeremy A. Miller, Marmar Moussa, Joseph R. Nery, Philip R. Nicovich, Sheng Yong Niu, Joshua Orvis, Julia K. Osteen, Scott Owen, Carter R. Palmer, Thanh Pham, Nongluk Plongthongkum, Olivier Poirion, Nora M. Reed, Christine Rimorin, Angeline Rivkin, William J. Romanow, Adriana E. Sedeño-Cortés, Kimberly Siletti, Saroja Somasundaram, Josef Sulc, Michael Tieu, Amy Torkelson, Herman Tung, Xinxin Wang, Fangming Xie, Anna Marie Yanny, Renee Zhang, Seth A. Ament, M. Margarita Behrens, Hector Corrada Bravo, Jerold Chun, Alexander Dobin, Jesse Gillis, Ronna Hertzano, Patrick R. Hof, Thomas Höllt, Gregory D. Horwitz, C. Dirk Keene, Peter V. Kharchenko, Andrew L. Ko, Boudewijn P. Lelieveldt, Chongyuan Luo, Eran A. Mukamel, António Pinto-Duarte, Sebastian Preissl, Aviv Regev, Bing Ren, Richard H. Scheuermann, Kimberly Smith, William J. Spain, Owen R. White, Christof Koch, Michael Hawrylycz, Bosiljka Tasic, Evan Z. Macosko, Steven A. McCarroll, Jonathan T. Ting, Hongkui Zeng, Kun Zhang, Guoping Feng, Joseph R. Ecker, Sten Linnarsson, Ed S. Lein

Research output: Contribution to journalArticlepeer-review

67 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)111-119
Number of pages9
JournalNature
Volume598
Issue number7879
DOIs
StatePublished - Oct 7 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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