Identification Of The Potential Hair Cell Regeneration Ability Of Apical Lgr5+ Cells In The Neonatal Murine Cochlea

Supporting cells(SCs)in the mouse inner ear are reliable source for hair cell(HC)regeneration after damage.Lgr5+ SCs have been shown as the enriched HC progenitors in the cochlea,thus it is important to understand the detailed mechanism regulating these progenitor cells’ proliferation and differentiation.Multiple studies have shown a difference in the proliferation and HC regeneration ability of SCs between the apical and basal turns.However,the detailed differences between the transcriptomes of the apical and basal Lgr5+ SCs have not yet been investigated.Here,we show that when isolated by flowcytometry,Lgr5+ cells from the apex generated significantly more HCs and had significantly higher proliferation and mitotic HC regeneration ability compared to those from the base.Also the Lgr5+ cells from the apex exhibited a greater rate of expansion upon multiple passaging of neurosphere,which shows their higher ability to self-renew and proliferate.Next,we used microarray analysis to determine the transcriptome expression profiles of Lgr5+ progenitors from the apex and the base.We first analyzed the genes enriched and differentially expressed in Lgr5+ progenitors from the apex and the base.Then we analyzed the cell cycle genes and the transcription factors that might regulate the proliferation and differentiation of Lgr5+ progenitors.Lastly,to further analyze the role of differentially expressed genes and to gain an overall view of the gene network in cochlear HC regeneration,we created a protein-protein interaction network.Together,our datasets suggest the possible genes that might regulate the proliferation and HC regeneration ability of Lgr5+ progenitors,and these genes might provide new therapeutic targets for HC regeneration in the future.