Abstract

Loss of sensory hair cells leads to deafness and balance deficiencies. In contrast to mammalian hair cells, zebrafish ear and lateral line hair cells regenerate from poorly characterized support cells. Equally ill-defined is the gene regulatory network underlying the progression of support cells to differentiated hair cells. scRNA-Seq of lateral line organs uncovered five different support cell types, including quiescent and activated stem cells. Ordering of support cells along a developmental trajectory identified self-renewing cells and genes required for hair cell differentiation. scRNA-Seq analyses of fgf3 mutants, in which hair cell regeneration is increased, demonstrates that Fgf and Notch signaling inhibit proliferation of support cells in parallel by inhibiting Wnt signaling. Our scRNA-Seq analyses set the foundation for mechanistic studies of sensory organ regeneration and is crucial for identifying factors to trigger hair cell production in mammals. The data is searchable and publicly accessible via a web-based interface.

Data availability

BAM files and count matrices produced by Cell Ranger have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE123241)

The following data sets were generated

Article and author information

Author details

  1. Mark E Lush

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Daniel C Diaz

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Nina Koenecke

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sungmin Baek

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Helena Boldt

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Madeleine K St Peter

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Tatiana Gaitan-Escudero

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Andres Romero-Carvajal

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2570-1749
  9. Elisabeth M Busch-Nentwich

    Wellcome Sanger Institute, Hinxton, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6450-744X
  10. Anoja G Perera

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Kathryn E Hall

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Allison Peak

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Jeffrey S Haug

    Stowers Institute for Medical Research, Kansas City, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Tatjana Piotrowski

    Stowers Institute for Medical Research, Kansas City, United States
    For correspondence
    pio@stowers.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8098-2574

Funding

National Institute on Deafness and Other Communication Disorders (1R01DC015488-01A1)

  • Tatjana Piotrowski

Hearing Health Foundation

  • Tatjana Piotrowski

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

Reviewing Editor

  1. Tanya T Whitfield, University of Sheffield, United Kingdom

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. All of the animals were handled according to approved institutional animal care use committee (IACUC) protocol (#2017-0176) of the Stowers Institute for Medical Research.

Version history

  1. Received: December 15, 2018
  2. Accepted: January 24, 2019
  3. Accepted Manuscript published: January 25, 2019 (version 1)
  4. Version of Record published: February 5, 2019 (version 2)
  5. Version of Record updated: April 17, 2019 (version 3)

Copyright

© 2019, Lush 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. Mark E Lush
  2. Daniel C Diaz
  3. Nina Koenecke
  4. Sungmin Baek
  5. Helena Boldt
  6. Madeleine K St Peter
  7. Tatiana Gaitan-Escudero
  8. Andres Romero-Carvajal
  9. Elisabeth M Busch-Nentwich
  10. Anoja G Perera
  11. Kathryn E Hall
  12. Allison Peak
  13. Jeffrey S Haug
  14. Tatjana Piotrowski
(2019)
scRNA-Seq reveals distinct stem cell populations that drive hair cell regeneration after loss of Fgf and Notch signaling
eLife 8:e44431.
https://doi.org/10.7554/eLife.44431

Share this article

https://doi.org/10.7554/eLife.44431

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