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Elife. 2019 Jan 25;8. pii: e44431. doi: 10.7554/eLife.44431.

scRNA-Seq reveals distinct stem cell populations that drive hair cell regeneration after loss of Fgf and Notch signaling.

Author information

1
Stowers Institute for Medical Research, Kansas City, United States.
2
Pontificia Universidad Catolica del Ecuador, Ciencias Biologicas, Quito, Ecuador.
3
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom.
4
Department of Medicine, University of Cambridge, Cambridge, United Kingdom.
#
Contributed equally

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.

KEYWORDS:

developmental biology; hearing; lateral line system; regeneration; regenerative medicine; sensory hair cells; single cell RNA-Seq; stem cells; zebrafish

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