Characterization of Wnt and Notch-Responsive Lgr5+ Hair Cell Progenitors in the Striolar Region of the Neonatal Mouse Utricle

Frontiers in Molecular Neuroscience
Dan YouHuawei Li

Abstract

Dysfunctions in hearing and balance are largely connected with hair cell (HC) loss. Although regeneration of HCs in the adult cochlea does not occur, there is still limited capacity for HC regeneration in the mammalian utricle from a distinct population of supporting cells (SCs). In response to HC damage, these Lgr5+ SCs, especially those in the striolar region, can regenerate HCs. In this study, we isolated Lgr5+ SCs and Plp1+ SCs (which originate from the striolar and extrastriolar regions, respectively) from transgenic mice by flow cytometry so as to compare the properties of these two subsets of SCs. We found that the Lgr5+ progenitors had greater proliferation and HC regeneration ability than the Plp1+ SCs and that the Lgr5+ progenitors responded more strongly to Wnt and Notch signaling than Plp1+ SCs. We then compared the gene expression profiles of the two populations by RNA-Seq and identified several genes that were significantly differentially expressed between the two populations, including genes involved in the cell cycle, transcription and cell signaling pathways. Targeting these genes and pathways might be a potential way to activate HC regeneration.

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Citations

Aug 4, 2020·World Journal of Stem Cells·María Beatriz Durán-Alonso
Aug 21, 2019·Frontiers in Molecular Neuroscience·Shasha ZhangRenjie Chai
Mar 2, 2021·Frontiers in Cell and Developmental Biology·Mingxuan WuHuawei Li

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Methods Mentioned

BETA
flow cytometry
RNA-Seq
genotyping
fluorescence activated cell sorting
transgenic
PCR
Assay
FACS

Software Mentioned

Fastq
ImageJ
Trimmomatic
STRING
Adobe Photoshop
GraphPad Prism
Primer3
DAVID
Cufflinks
TopHat

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