Single-cell transcriptomic profiling of the zebrafish inner ear reveals molecularly distinct hair cell and supporting cell subtypes

  1. Tuo Shi
  2. Marielle O Beaulieu
  3. Lauren M Saunders
  4. Peter Fabian
  5. Cole Trapnell
  6. Neil Segil
  7. J Gage Crump  Is a corresponding author
  8. David W Raible  Is a corresponding author
  1. University of Southern California, United States
  2. University of Washington, United States

Abstract

A major cause of human deafness and vestibular dysfunction is permanent loss of the mechanosensory hair cells of the inner ear. In non-mammalian vertebrates such as zebrafish, regeneration of missing hair cells can occur throughout life. While a comparative approach has the potential to reveal the basis of such differential regenerative ability, the degree to which the inner ears of fish and mammals share common hair cells and supporting cell types remains unresolved. Here we perform single-cell RNA sequencing of the zebrafish inner ear at embryonic through adult stages to catalog the diversity of hair cells and non-sensory supporting cells. We identify a putative progenitor population for hair cells and supporting cells, as well as distinct hair and supporting cell types in the maculae versus cristae. The hair cell and supporting cell types differ from those described for the lateral line system, a distributed mechanosensory organ in zebrafish in which most studies of hair cell regeneration have been conducted. In the maculae, we identify two subtypes of hair cells that share gene expression with mammalian striolar or extrastriolar hair cells. In situ hybridization reveals that these hair cell subtypes occupy distinct spatial domains within the three macular organs, the utricle, saccule, and lagena, consistent with the reported distinct electrophysiological properties of hair cells within these domains. These findings suggest that primitive specialization of spatially distinct striolar and extrastriolar hair cells likely arose in the last common ancestor of fish and mammals. The similarities of inner ear cell type composition between fish and mammals validate zebrafish as a relevant model for understanding inner ear-specific hair cell function and regeneration.

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Sequencing data have been deposited in GEO under accession codes

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The following previously published data sets were used

Article and author information

Author details

  1. Tuo Shi

    Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5268-0146
  2. Marielle O Beaulieu

    Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Lauren M Saunders

    Department of Genomic Sciences, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4377-4252
  4. Peter Fabian

    Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Cole Trapnell

    Department of Genomic Sciences, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Neil Segil

    Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0441-2067
  7. J Gage Crump

    Department of Stem Cell Biology and Regenerative Medicine, University of Southern California, Los Angeles, United States
    For correspondence
    gcrump@med.usc.edu
    Competing interests
    The authors declare that no competing interests exist.
  8. David W Raible

    Department of Biological Structure, University of Washington, Seattle, United States
    For correspondence
    draible@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5342-5841

Funding

National Institute on Deafness and Other Communication Disorders (R21DC019948)

  • David W Raible

National Institute of Dental and Craniofacial Research (R35DE027550)

  • J Gage Crump

National Institute on Deafness and Other Communication Disorders (R01DC015829)

  • Neil Segil

National Institute on Deafness and Other Communication Disorders (T32DC009975)

  • Tuo Shi
  • Neil Segil

National Institute on Deafness and Other Communication Disorders (T32DC005361)

  • Marielle O Beaulieu
  • David W Raible

National Institute on Deafness and Other Communication Disorders (F31DC020898)

  • Marielle O Beaulieu

Hamilton and Mildred Kellogg Trust

  • David W Raible

The Whitcraft Family Gift

  • David W Raible

Hearing Health Foundation

  • David W Raible

Paul G. Allen Frontiers Group (Allen Discovery Center for Cell Lineage Tracing)

  • Cole Trapnell

National Human Genome Research Institute (UM1HG011586)

  • Cole Trapnell

National Human Genome Research Institute (1R01HG010632)

  • Cole Trapnell

National Institute on Deafness and Other Communication Disorders (F31DC020633)

  • Tuo Shi

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The Institutional Animal Care and Use Committees of the University of Southern California (Protocol 20771) and University of Washington (Protocol 2997-01) approved all animal experiments.

Copyright

© 2023, Shi 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. Tuo Shi
  2. Marielle O Beaulieu
  3. Lauren M Saunders
  4. Peter Fabian
  5. Cole Trapnell
  6. Neil Segil
  7. J Gage Crump
  8. David W Raible
(2023)
Single-cell transcriptomic profiling of the zebrafish inner ear reveals molecularly distinct hair cell and supporting cell subtypes
eLife 12:e82978.
https://doi.org/10.7554/eLife.82978

Share this article

https://doi.org/10.7554/eLife.82978

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