Single-cell transcriptomic profiling of the zebrafish inner ear reveals molecularly distinct hair cell and supporting cell subtypes
- University of Southern California, United States
- 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.
Data availability
Sequencing data have been deposited in GEO under accession codes
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Epithelial planar bipolarity emerges from Notch-mediated asymmetric inhibition of Emx2NCBI Gene Expression Omnibus, GSE144827.
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High-resolution single cell transcriptome analysis of zebrafish sensory hair cell regenerationNCBI Gene Expression Omnibus, GSE196211.
Article and author information
Author details
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.
Reviewing Editor
- Lavinia Sheets, Washington University School of Medicine in St Louis, United States
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.
Version history
- Received: August 25, 2022
- Preprint posted: September 10, 2022 (view preprint)
- Accepted: January 4, 2023
- Accepted Manuscript published: January 4, 2023 (version 1)
- Version of Record published: January 19, 2023 (version 2)
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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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
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