AAV‐mediated Gpm6b expression supports hair cell reprogramming

Author:

Sun Qiuhan1,Zhang Liyan1,Chen Tian1,Li Nianci1,Tan Fangzhi1,Gu Xingliang1,Zhou Yinyi1,Zhang Ziyu1,Lu Yicheng1,Lu Jie2,Qian Xiaoyun3,Guan Bing2,Qi Jieyu1,Ye Fanglei4,Chai Renjie15678ORCID

Affiliation:

1. State Key Laboratory of Digital Medical Engineering, Department of Otolaryngology Head and Neck Surgery, Zhongda Hospital, School of Life Sciences and Technology, Advanced Institute for Life and Health, Jiangsu Province High‐Tech Key Laboratory for Bio‐Medical Research Southeast University Nanjing China

2. Northern Jiangsu People's Hospital Affiliated to Yangzhou University/Clinical Medical College Yangzhou University Yangzhou China

3. Department of Otolaryngology‐Head and Neck Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School Jiangsu Provincial Key Medical Discipline(Laboratory) Nanjing China

4. Department of Otology The First Affiliated Hospital of Zhengzhou University Zhengzhou Henan China

5. Department of Otolaryngology Head and Neck Surgery, Sichuan Provincial People's Hospital University of Electronic Science and Technology of China Chengdu China

6. Co‐Innovation Center of Neuroregeneration Nantong University Nantong China

7. Institute for Stem Cells and Regeneration Chinese Academy of Science Beijing China

8. Southeast University Shenzhen Research Institute Shenzhen China

Abstract

AbstractIrreversible 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.

Funder

Science and Technology Department of Sichuan Province

Fundamental Research Funds for the Central Universities

National Key Research and Development Program of China

National Natural Science Foundation of China

Publisher

Wiley

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