Mapping the transcriptional diversity of genetically and anatomically defined cell populations in the mouse brain

Abstract

Understanding the principles governing neuronal diversity is a fundamental goal for neuroscience. Here we provide an anatomical and transcriptomic database of nearly 200 genetically identified cell populations. By separately analyzing the robustness and pattern of expression differences across these cell populations, we identify two gene classes contributing distinctly to neuronal diversity. Short homeobox transcription factors distinguish neuronal populations combinatorially, and exhibit extremely low transcriptional noise, enabling highly robust expression differences. Long neuronal effector genes, such as channels and cell adhesion molecules, contribute disproportionately to neuronal diversity, based on their patterns rather than robustness of expression differences. By linking transcriptional identity to genetic strains and anatomical atlases we provide an extensive resource for further investigation of mouse neuronal cell types.

Data availability

Sequencing data have been deposited in NCBI GEO under accession number GSE79238.

The following data sets were generated
The following previously published data sets were used
    1. Tasic B et al
    (2018) Cell Diversity in the Mouse Cortex
    Available at http://celltypes.brain-map.org/rnaseq.

Article and author information

Author details

  1. Ken Sugino

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    For correspondence
    ken.sugino@gmail.com
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5795-0635
  2. Erin Clark

    Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4013-325X
  3. Anton Schulmann

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yasuyuki Shima

    Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Lihua Wang

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. David L Hunt

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Bryan M Hooks

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0135-4284
  8. Dimitri Traenkner

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Jayaram Chandrashekar

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6412-0114
  10. Serge Picard

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Andrew L Lemire

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Nelson Spruston

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3118-1636
  13. Adam W Hantman

    Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Sacha B Nelson

    Brandeis University, Waltham, United States
    For correspondence
    nelson@brandeis.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0108-8599

Funding

Howard Hughes Medical Institute

  • Ken Sugino
  • Anton Schulmann
  • Lihua Wang
  • David L Hunt
  • Bryan M Hooks
  • Dimitri Traenkner
  • Jayaram Chandrashekar
  • Andrew L Lemire
  • Nelson Spruston
  • Adam W Hantman
  • Sacha B Nelson

National Eye Institute (EY022360)

  • Erin Clark
  • Yasuyuki Shima
  • Sacha B Nelson

National Institute of Mental Health (MH105949)

  • Erin Clark
  • Yasuyuki Shima
  • Sacha B Nelson

National Institute of Neurological Disorders and Stroke (NS075007)

  • Erin Clark
  • Yasuyuki Shima
  • Sacha B Nelson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were conducted in accordance with the requirements of theInstitutional Animal Care and Use Committees at Janelia Research Campus (protocol# not available) and Brandeis University (protocol#17001).

Reviewing Editor

  1. Chris P Ponting, University of Edinburgh, United Kingdom

Version history

  1. Received: July 20, 2018
  2. Accepted: April 11, 2019
  3. Accepted Manuscript published: April 12, 2019 (version 1)
  4. Version of Record published: May 3, 2019 (version 2)

Copyright

© 2019, Sugino et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Ken Sugino
  2. Erin Clark
  3. Anton Schulmann
  4. Yasuyuki Shima
  5. Lihua Wang
  6. David L Hunt
  7. Bryan M Hooks
  8. Dimitri Traenkner
  9. Jayaram Chandrashekar
  10. Serge Picard
  11. Andrew L Lemire
  12. Nelson Spruston
  13. Adam W Hantman
  14. Sacha B Nelson
(2019)
Mapping the transcriptional diversity of genetically and anatomically defined cell populations in the mouse brain
eLife 8:e38619.
https://doi.org/10.7554/eLife.38619

Share this article

https://doi.org/10.7554/eLife.38619

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