AAV-mediated Gpm6b expression supports hair cell reprogramming
Qiuhan Sun , Liyan Zhang , Tian Chen , Nianci Li , Fangzhi Tan , Xingliang Gu , Yinyi Zhou , Ziyu Zhang , Yicheng Lu , Jie Lu , Xiaoyun Qian , Bing Guan , Jieyu Qi , Fanglei Ye , Renjie Chai
Cell Proliferation ›› 2024, Vol. 57 ›› Issue (7) : e13620
AAV-mediated Gpm6b expression supports hair cell reprogramming
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.
2024 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.
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