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AAV-mediated Gpm6b expression supports hair cell reprogramming.
Qiuhan Sun1, Liyan Zhang1, Tian Chen1
1State 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.
Neuron membrane glycoprotein M6B (Gpm6b) overexpression promotes hair cell regeneration in the cochlea. This finding offers a promising therapeutic target for hearing repair by enhancing inner ear stem cell potential.
Area of Science:
- Oto-neurology
- Regenerative Medicine
- Molecular Biology
Background:
- Hair cell (HC) damage in the cochlea causes irreversible hearing loss.
- Cochlear supporting cells (SCs) possess the potential to regenerate into HCs.
- Neuron membrane glycoprotein M6B (Gpm6b) is implicated as a regulator of HC regeneration.
Purpose of the Study:
- To investigate the role of Gpm6b in promoting HC regeneration.
- To evaluate the therapeutic potential of Gpm6b overexpression for hearing repair.
Main Methods:
- Adeno-associated virus (AAV-ie) mediated Gpm6b overexpression in murine cochlear models.
- Assessment of SC-derived organoid expansion and SC plasticity.
- In vivo studies involving round window membrane injection for Gpm6b delivery to the organ of Corti.
Main Results:
- AAV-ie-mediated Gpm6b overexpression significantly promoted SC-derived organoid expansion.
- Enhanced Gpm6b expression maintained SC plasticity, enabling cell cycle re-entry and SC-to-HC differentiation.
- In vivo Gpm6b overexpression facilitated the trans-differentiation of Lgr5+ SCs into HCs in the organ of Corti.
Conclusions:
- Gpm6b overexpression is a potent driver of HC regeneration.
- Targeting Gpm6b presents a promising strategy for hearing restoration therapies.
- Combining inner ear stem cell approaches with AAV-mediated Gpm6b delivery shows therapeutic potential.
