Single cell RNA-Seq reveals distinct stem cell populations that drive sensory hair cell regeneration in response to loss of Fgf and Notch signaling; Distinct progenitor populations mediate regeneration in the zebrafish lateral line.

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.

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Single cell RNA-Seq reveals distinct stem cell populations that drive sensory hair cell regeneration in response to loss of Fgf and Notch signaling

10.1101/496612 ◽

2018 ◽

Author(s):

Mark E. Lush ◽

Daniel C. Diaz ◽

Nina Koenecke ◽

Sungmin Baek ◽

Helena Boldt ◽

...

Keyword(s):

Hair Cell ◽

Notch Signaling ◽

Single Cell ◽

Lateral Line ◽

Hair Cells ◽

Developmental Trajectory ◽

Cell Regeneration ◽

Hair Cell Regeneration ◽

Specific Expression ◽

Sensory Hair

AbstractLoss 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, proliferating support cells. Equally ill-defined is the gene regulatory network underlying the progression of support cells to cycling hair cell progenitors and differentiated hair cells. We used single cell RNA-Sequencing (scRNA-Seq) of lateral line sensory organs and uncovered five different support cell types, including quiescent and activated stem cells. In silico ordering of support cells along a developmental trajectory identified cells that self-renew and new groups of 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. As a resource, we implemented a shiny application that allows the community to interrogate cell type specific expression of genes of interest.

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Faculty Opinions recommendation of Identification of modulators of hair cell regeneration in the zebrafish lateral line.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.714447804.790002804 ◽

2012 ◽

Author(s):

Andy Groves

Keyword(s):

Hair Cell ◽

Lateral Line ◽

Cell Regeneration ◽

Hair Cell Regeneration

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