Evolution of cellular diversity in primary motor cortex of human, marmoset monkey, and mouse

Abstract: 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.

Trygve E. Bakken, Nicholas L. Jorstad, Qiwen Hu, Blue B. Lake, Wei Tian, et al. Evolution of cellular diversity in primary motor cortex of human, marmoset monkey, and mouse. BioRxiv, 2020.
@article { bib:2020_cellular_diversity_evolution,
author = { Trygve E. Bakken and Nicholas 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 Anup Mahurkar and Delissa McMillen and Jeremy A. Miller and Marmar Moussa and Joseph R. Nery and Joshua Orvis 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 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 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 Hawlrylycz 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 = { Evolution of cellular diversity in primary motor cortex of human, marmoset monkey, and mouse },
year = { 2020 },
doi = { 10.1101/2020.03.31.016972 },