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.
Highlights
Balance in mammals is maintained by the activity in a subdivision of the inner ear known as the vestibular system, and the primary organ involved in balance is the utricle
Several studies have shown that new hair cell (HC) regeneration can occur after HC damage to restore the function of the utricle (Li et al, 2003; Lin et al, 2011; Wang et al, 2015), Identify supporting cells (SCs) in Utricle and increasing evidence suggests that utricular SCs serve as a reliable source to partially regenerate HCs either via direct trans-differentiation or by mitotic regeneration (Sinkkonen et al, 2011)
It has been reported that the SCs of the mammalian utricle have a limited capacity for HC regeneration in response to HC damage (Li et al, 2003), and the striolar region is generally recognized as the most conducive area for HC regeneration
Summary
Balance in mammals is maintained by the activity in a subdivision of the inner ear known as the vestibular system, and the primary organ involved in balance is the utricle. Several studies have shown that new HC regeneration can occur after HC damage to restore the function of the utricle (Li et al, 2003; Lin et al, 2011; Wang et al, 2015), Identify SCs in Utricle and increasing evidence suggests that utricular SCs serve as a reliable source to partially regenerate HCs either via direct trans-differentiation or by mitotic regeneration (Sinkkonen et al, 2011). For the purpose of restoring full utricular function, several studies have made efforts to promote SC proliferation and HC regeneration (Lin et al, 2011; Burns et al, 2012b), and identifying genes that regulate the proliferation and HC regeneration ability of SCs is very important for developing new therapeutic strategies for HC regeneration
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