Comparative cellular analysis of motor cortex in human, marmoset and mouse
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.
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@article{ bib:2020_cellular_diversity_evolution,
author = {Trygve E. Bakken and Nikolas L. Jorstad and Qiwen Hu and Blue B. Lake and Wei Tian and Brian E. Kalmbach and Megan Crow and Rebecca D. Hodge and Fenna M. Krienen and Staci A. Sorensen and Jeroen Eggermont and Zizhen Yao and Brian D. Aevermann and Andrew I. Aldridge and Anna Bartlett and Darren Bertagnolli and Tamara Casper and Rosa G. Castanon and Kirsten Crichton and Tanya L. Daigle and Rachel Dalley and Nick Dee and Nikolai Dembrow and Dinh Diep and Song-Lin Ding and Weixiu Dong and Rongxin Fang and Stephan Fischer and Melissa Goldman and Jeff Goldy and Lucas T. Graybuck and Brian R. Herb and Xiaomeng Hou and Jayaram Kancherla and Matthew Kroll and Kanan Lathia and Baldur van Lew and Yang Eric Li and Christine S. Liu and Hanqing Liu and Jacinta D. Lucero and Anup Mahurkar and Delissa McMillen and Jeremy A. Miller and Marmar Moussa and Joseph R. Nery and Philip R. Nicovich and Sheng-Yong Niu and Joshua Orvis and Julia K. Osteen and Scott Owen and Carter R. Palmer and Thanh Pham and Nongluk Plongthongkum and Olivier Poirion and Nora M. Reed and Christine Rimorin and Angeline Rivkin and William J. Romanow and Adriana E. Sede{\~n}o-Cort{\s and Kimberly Siletti and Saroja Somasundaram and Josef Sulc and Michael Tieu and Amy Torkelson and Herman Tung and Xinxin Wang and Fangming Xie and Anna Marie Yanny and Renee Zhang and Seth A. Ament and M. Margarita Behrens and Hector Corrada Bravo and Jerold Chun and Alexander Dobin and Jesse Gillis and Ronna Hertzano and Patrick R. Hof and Thomas H{\"o}llt and Gregory D. Horwitz and C. Dirk Keene and Peter V. Kharchenko and Andrew L. Ko and Boudewijn Lelieveldt and Chongyuan Luo and Eran A. Mukamel and Ant{\nio Pinto-Duarte and Sebastian Preissl and Aviv Regev and Bing Ren and Richard H. Scheuermann and Kimberly Smith and William J. Spain and Owen R. White and Christof Koch and Michael Hawrylycz and Bosiljka Tasic and Evan Z. Macosko and Steven A. McCarroll and Jonathan T. Ting and Hongkui Zeng and Kun Zhang and Guoping Feng and Joseph R. Ecker and Sten Linnarsson and Ed S. Lein},
title = { Comparative cellular analysis of motor cortex in human, marmoset and mouse },
journal = { Nature },
volume = { 598 },
pages = { 111 -- 119 },
year = { 2021 },
doi = { 10.1038/s41586-021-03465-8 },
}