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

Trygve Bakken, Nicholas L. Jorstad, Qiwen Hu, Blue B. Lake, Wei Tian, Brian E. Kalmbach, Megan Crow, Rebecca Hodge, Fenna M. Krienen, Staci A. Sorensen, Jeroen Eggermont, Zizhen Yao, Brian Aevermann, Andrew I. Aldridge, Anna Bartlett, Darren Bertagnolli, Tamara Casper, Rosa G. Castanon, Kirsten Crichton, Tanya L. Daigle, Rachel Dalley, Nick Dee, Nikolai Dembrow, Dinh Diep, Song-Lin Ding, Weixiu Dong, Rongxin Fang, Stephan Fischer, Melissa Goldman, Jeff Goldy, Lucas Graybuck, Brian R. Herb, Xiaomeng Hou, Jayaram Kancherla, Matthew Kroll, Kanan Lathia, Baldur van Lew, Yang Eric Li, Christine S. Liu, Hanqing Liu, Anup Mahurkar, Delissa McMillen, Jeremy Miller, Marmar Moussa, Joseph R. Nery, Joshua Orvis, 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, Hector Corrada Bravo, Jerold Chun, Alexander Dobin, Jesse Gillis, Ronna Hertzano, Patrick R. Hof, Thomas Höllt, Gregory D. Horwitz, Dirk Keene, Peter V. Kharchenko, Andrew Ko, Boudewijn P.F. Lelieveldt, Chongyuan Luo, Eran A. Mukamel, Sebastian Preissl, Aviv Regev, Bing Ren, Richard 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 Lein
Nature, Volume 598, page 111-119 - 2021
Download the publication : 2020_cellular_diversity_evolution.pdf [31.6Mo]  
The primary motor cortex (M1) is essential for voluntary fine-motor control and is functionally conserved across mammals. 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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  author       = "Bakken, Trygve and Jorstad, Nicholas L. and Hu, Qiwen and Lake, Blue B. and Tian, Wei and Kalmbach, Brian E.
                  and Crow, Megan and Hodge, Rebecca and Krienen, Fenna M. and Sorensen, Staci A. and Eggermont, Jeroen and Yao,
                  Zizhen and Aevermann, Brian and Aldridge, Andrew I. and Bartlett, Anna and Bertagnolli, Darren and Casper,
                  Tamara and Castanon, Rosa G. and Crichton, Kirsten and Daigle, Tanya L. and Dalley, Rachel and Dee, Nick and
                  Dembrow, Nikolai and Diep, Dinh and Ding, Song-Lin and Dong, Weixiu and Fang, Rongxin and Fischer, Stephan and
                  Goldman, Melissa and Goldy, Jeff and Graybuck, Lucas and Herb, Brian R. and Hou, Xiaomeng and Kancherla,
                  Jayaram and Kroll, Matthew and Lathia, Kanan and Lew, Baldur van and Li, Yang Eric and Liu, Christine S. and
                  Liu, Hanqing and Mahurkar, Anup and McMillen, Delissa and Miller, Jeremy and Moussa, Marmar and Nery, Joseph
                  R. and Orvis, Joshua and Owen, Scott and Palmer, Carter R. and Pham, Thanh and Plongthongkum, Nongluk and
                  Poirion, Olivier and Reed, Nora M. and Rimorin, Christine and Rivkin, Angeline and Romanow, William J. and
                  Sedeño-Cortés, Adriana E. and Siletti, Kimberly and Somasundaram, Saroja and Sulc, Josef and Tieu,
                  Michael and Torkelson, Amy and Tung, Herman and Wang, Xinxin and Xie, Fangming and Yanny, Anna Marie and
                  Zhang, Renee and Ament, Seth A. and Corrada Bravo, Hector and Chun, Jerold and Dobin, Alexander and Gillis,
                  Jesse and Hertzano, Ronna and Hof, Patrick R. and H\öllt, Thomas and Horwitz, Gregory D. and Keene, Dirk
                  and Kharchenko, Peter V. and Ko, Andrew and Lelieveldt, Boudewijn P.F. and Luo, Chongyuan and Mukamel, Eran A.
                  and Preissl, Sebastian and Regev, Aviv and Ren, Bing and Scheuermann, Richard and Smith, Kimberly and Spain,
                  William J. and White, Owen R. and Koch, Christof and Hawrylycz, Michael and Tasic, Bosiljka and Macosko, Evan
                  Z. and McCarroll, Steven A. and Ting, Jonathan T. and Zeng, Hongkui and Zhang, Kun and Feng, Guoping and
                  Ecker, Joseph R. and Linnarsson, Sten and Lein, Ed",
  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",
  url          = ""