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

Authors:
Top Cited Papers
Open Access
Publisher website
Google Scholar
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.
All Related Versions
Funding Information
  • National Institute on Deafness and Other Communication Disorders (R21DC019948)
  • National Institute of Dental and Craniofacial Research (R35DE027550)
  • National Institute on Deafness and Other Communication Disorders (R01DC015829)
  • National Institute on Deafness and Other Communication Disorders (T32DC009975)
  • National Institute on Deafness and Other Communication Disorders (T32DC005361)
  • National Institute on Deafness and Other Communication Disorders (F31DC020898)
  • Hamilton and Mildred Kellogg Trust
  • The Whitcraft Family Gift
  • Hearing Health Foundation
  • Paul G. Allen Frontiers Group (Allen Discovery Center for Cell Lineage Tracing)
  • National Human Genome Research Institute (UM1HG011586)
  • National Human Genome Research Institute (1R01HG010632)
  • National Institute on Deafness and Other Communication Disorders (F31DC020633)

This publication has 97 references indexed in Scilit: