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Irreversible damage to hair cells (HCs) in the cochlea leads to hearing loss. Cochlear supporting cells (SCs) in the murine cochlea have the potential to differentiate into HCs. Neuron membrane glycoprotein M6B (Gpm6b) as a four‐transmembrane protein is a potential regulator of HC regeneration according to our previous research. In this study, we found that AAV‐ie‐mediated Gpm6b overexpression promoted SC‐derived organoid expansion. Enhanced Gpm6b prevented the normal decrease in SC plasticity as the cochlea develops by supporting cells re‐entry cell cycle and facilitating the SC‐to‐HC transformation. Also, overexpression of Gpm6b in the organ of Corti through the round window membrane injection facilitated the trans‐differentiation of Lgr5+ SCs into HCs. In conclusion, our results suggest that Gpm6b overexpression promotes HC regeneration and highlights a promising target for hearing repair using the inner ear stem cells combined with AAV. [ABSTRACT FROM AUTHOR]

Sensorineural hearing loss a result from hair cell damage, which is irreversible in mammals owing to the lack of hair cell regeneration, but recent researches have shown that Lgr5+ supporting cells are progenitors capable of regenerating hair cells. RPS14 (ribosomal protein S14) is a 40S ribosomal subunit component and is associated with erythrocyte differentiation, and in this study, we used a novel adeno‐associated virus‐inner ear system to upregulate Rps14 expression in cultured hair cell progenitors and observed an enhancement on their ability to proliferate and differentiate into hair cells. Similarly, Rps14 overexpression in the mice cochlea could promote supporting cells proliferation by activating the Wnt signalling pathway. In addition, over‐expressing Rps14 induced hair cells regeneration in the organ of Corti, and lineage tracing showed that the new hair cells had transformed from Lgr5+ progenitors. In conclusion, our analysis reveals the potential role of Rps14 in driving hair cell regeneration in mammalian. [ABSTRACT FROM AUTHOR]

The cover image is based on the article Pcolce2 overexpression promotes supporting cell reprogramming in the neonatal mouse cochlea by Changling Xu et al., https://doi.org/10.1111/cpr.13633. [ABSTRACT FROM AUTHOR]