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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-10-06

AUTHORS

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. Daigle, Rachel 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

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. More... »

PAGES

111-119

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  • Journal

    TITLE

    Nature

    ISSUE

    7879

    VOLUME

    598

    Author Affiliations

  • Allen Institute for Brain Science, Seattle, WA, USA
  • Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA
  • Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA
  • The Salk Institute for Biological Studies, La Jolla, CA, USA
  • Department of Physiology and Biophysics, University of Washington, Seattle, WA, USA
  • Stanley Institute for Cognitive Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
  • Department of Genetics, Harvard Medical School, Boston, MA, USA
  • LKEB, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
  • J. Craig Venter Institute, La Jolla, CA, USA
  • Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA
  • Epilepsy Center of Excellence, Department of Veterans Affairs Medical Center, Seattle, WA, USA
  • Bioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA, USA
  • Institute for Genomes Sciences, University of Maryland School of Medicine, Baltimore, MD, USA
  • Center for Epigenomics, Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA
  • Department of Computer Science, University of Maryland College Park, College Park, MD, USA
  • Ludwig Institute for Cancer Research, La Jolla, CA, USA
  • Biomedical Sciences Program, School of Medicine, University of California, San Diego, La Jolla, CA, USA
  • University of Connecticut, Storrs, CT, USA
  • Computer Science and Engineering Program, University of California, San Diego, La Jolla, CA, USA
  • Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA
  • Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
  • McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO, USA
  • Department of Physics, University of California, San Diego, La Jolla, CA, USA
  • Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA
  • Departments of Otorhinolaryngology, Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
  • Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Computer Graphics and Visualization Group, Delt University of Technology, Delft, The Netherlands
  • Department of Physiology and Biophysics, Washington National Primate Research Center, University of Washington, Seattle, WA, USA
  • Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA
  • Regional Epilepsy Center, Harborview Medical Center, Seattle, WA, USA
  • Pattern Recognition and Bioinformatics group, Delft University of Technology, Delft, The Netherlands
  • Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA, USA
  • Department of Cognitive Science, University of California, San Diego, La Jolla, CA, USA
  • Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA, USA
  • Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41586-021-03465-8

    DOI

    http://dx.doi.org/10.1038/s41586-021-03465-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1141640979

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34616062


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