AAV-mediated Gpm6b expression supports hair cell reprogramming

被引：8
|
作者：
Sun, Qiuhan [1 ]
Zhang, Liyan [1 ]
Chen, Tian [1 ]
Li, Nianci [1 ]
Tan, Fangzhi [1 ,9 ]
Gu, Xingliang [1 ]
Zhou, Yinyi [1 ]
Zhang, Ziyu [1 ]
Lu, Yicheng [1 ]
Lu, Jie [2 ]
Qian, Xiaoyun [3 ]
Guan, Bing [2 ,10 ]
Qi, Jieyu [1 ,9 ]
Ye, Fanglei [4 ,11 ]
Chai, Renjie [1 ,5 ,6 ,7 ,8 ,9 ]
机构：
[1] Southeast Univ, Zhongda Hosp, Adv Inst Life & Hlth, Sch Life Sci & Technol,State Key Lab Digital Med E, Nanjing, Peoples R China
[2] Yangzhou Univ, Northern Jiangsu Peoples Hosp, Clin Med Coll, Yangzhou, Peoples R China
[3] Nanjing Univ, Dept Otolaryngol Head & Neck Surg, Affiliated Drum Tower Hosp, Jiangsu Prov Key Med Discipline Lab,Med Sch, Nanjing, Peoples R China
[4] Zhengzhou Univ, Dept Otol, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China
[5] Univ Elect Sci & Technol China, Sichuan Prov Peoples Hosp, Dept Otolaryngol Head & Neck Surg, Chengdu, Peoples R China
[6] Nantong Univ, Coinnovat Ctr Neuroregenerat, Nantong, Peoples R China
[7] Chinese Acad Sci, Inst Stem Cells & Regenerat, Beijing, Peoples R China
[8] Southeast Univ, Shenzhen Res Inst, Shenzhen, Peoples R China
[9] Southeast Univ, Zhongda Hosp, Adv Inst Life & Hlth, Sch Life Sci & Technol,State Key Lab Digital Med E, Nanjing 210096, Peoples R China
[10] Yangzhou Univ, Clin Med Coll, Northern Jiangsu Peoples Hosp, Yangzhou 225001, Peoples R China
[11] Zhengzhou Univ, Dept Otol, Affiliated Hosp 1, Zhengzhou 450000, Henan, Peoples R China
来源：
CELL PROLIFERATION | 2024年 / 57卷 / 07期
关键词：
GENE-THERAPY; WNT; DIFFERENTIATION; REGENERATION; INHIBITORS; COCHLEA; HEARING; GROWTH;
D O I：
10.1111/cpr.13620
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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.
引用
收藏
页数：12
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