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).

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.

Metrics

  • 7,416
    views
  • 1,073
    downloads
  • 71
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Further reading

    1. Neuroscience
    Li Shen, Shuo Li ... Yi Jiang
    Research Article

    When observing others’ behaviors, we continuously integrate their movements with the corresponding sounds to enhance perception and develop adaptive responses. However, how the human brain integrates these complex audiovisual cues based on their natural temporal correspondence remains unclear. Using electroencephalogram (EEG), we demonstrated that rhythmic cortical activity tracked the hierarchical rhythmic structures in audiovisually congruent human walking movements and footstep sounds. Remarkably, the cortical tracking effects exhibit distinct multisensory integration modes at two temporal scales: an additive mode in a lower-order, narrower temporal integration window (step cycle) and a super-additive enhancement in a higher-order, broader temporal window (gait cycle). Furthermore, while neural responses at the lower-order timescale reflect a domain-general audiovisual integration process, cortical tracking at the higher-order timescale is exclusively engaged in the integration of biological motion cues. In addition, only this higher-order, domain-specific cortical tracking effect correlates with individuals’ autistic traits, highlighting its potential as a neural marker for autism spectrum disorder. These findings unveil the multifaceted mechanism whereby rhythmic cortical activity supports the multisensory integration of human motion, shedding light on how neural coding of hierarchical temporal structures orchestrates the processing of complex, natural stimuli across multiple timescales.

    1. Evolutionary Biology
    2. Neuroscience
    Gregor Belušič
    Insight

    The first complete 3D reconstruction of the compound eye of a minute wasp species sheds light on the nuts and bolts of size reduction.