Characterization of the transcriptomes of Atoh1-induced hair cells in the mouse cochlea.

Abstract

Postnatal mammalian cochlear hair cells (HCs) can be regenerated by direct transdifferentiation or by mitotic regeneration from supporting cells through many pathways, including Atoh1, Wnt, Hedgehog and Notch signaling. However, most new HCs are immature HCs. In this study we used RNA-Seq analysis to compare the differences between the transcriptomes of Atoh1 overexpression-induced new HCs and the native HCs, and to define the factors that might help to promote the maturation of new HCs. As expected, we found Atoh1-induced new HCs had obvious HC characteristics as demonstrated by the expression of HC markers such as Pou4f3 and Myosin VIIA (Myo7a). However, Atoh1-induced new HCs had significantly lower expression of genes that are related to HC function such as Slc26a5 (Prestin), Slc17a8 and Otof. We found that genes related to HC cell differentiation and maturation (Kcnma1, Myo6, Myo7a, Grxcr1, Gfi1, Wnt5a, Fgfr1, Gfi1, Fgf8 etc.) had significantly lower expression levels in new HCs compared to native HCs. In conclusion, we found a set of genes that might regulate the differentiation and maturation of new HCs, and these genes might serve as potential new therapeutic targets for functional HC regeneration and hearing recovery.