scRNA-Seq reveals distinct stem cell populations that drive hair cell regeneration after loss of Fgf and Notch signaling
- Stowers Institute for Medical Research, United States
- Wellcome Sanger Institute, United Kingdom
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)
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Single cell RNA-Seq reveals Fgf signaling dynamics during sensory hair cell regenerationNCBI Gene Expression Omnibus, GSM3498552.
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Single cell RNA-Seq reveals Fgf signaling dynamics during sensory hair cell regenerationNCBI Gene Expression Omnibus, GSM3498553.
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Single cell RNA-Seq reveals Fgf signaling dynamics during sensory hair cell regenerationNCBI Gene Expression Omnibus, GSM3498554.
Article and author information
Author details
Andres Romero-Carvajal
Elisabeth M Busch-Nentwich
Tatjana Piotrowski
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.
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.
Reviewing Editor
- Tanya T Whitfield, University of Sheffield, United Kingdom
Version history
- Received: December 15, 2018
- Accepted: January 24, 2019
- Accepted Manuscript published: January 25, 2019 (version 1)
- Version of Record published: February 5, 2019 (version 2)
- 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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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
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