Hao Ming-Yu, Su Wei, Xu Jun-Yi, Chen Zhong-Rui, He Lu, Guo Jing-Ying, Liu Ke, Gong Shu-Sheng, Wang Guo-Peng
Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Clinical Center for Hearing Loss, Capital Medical University, Beijing, China.
Department of Otolaryngology-Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Clinical Center for Hearing Loss, Capital Medical University, Beijing, China.
Neurosci Lett. 2025 Feb 16;849:138136. doi: 10.1016/j.neulet.2025.138136. Epub 2025 Jan 28.
Hair cells (HCs) are essential for vestibular function, and irreversible damage to vestibular HCs in mammals is closely associated with vertigo. The stimulation of HC regeneration through exogenous gene delivery represents an ideal therapeutic approach for restoring vestibular function. Overexpression of Atoh1, Pou4f3, and Gfi1 (collectively referred to as APG) has demonstrated efficacy in promoting HC regeneration in the cochlea. However, the effects of APG on vestibular HC regeneration remain unclear. Here, we used adeno-associated virus-inner ear (AAVie) as a carrier to deliver APG to the utricles of neonatal mice and assessed the morphology and number of HCs and supporting cells (SCs) by immunofluorescence staining. GLAST;Rosa26 mouse line was used to trace SCs. The results showed that APG overexpression resulted in substantial SC transdifferentiation into HCs in the neonatal mouse utricle. Furthermore, APG overexpression maintained SC number by facilitating SC proliferation. Continuous Atoh1 overexpression caused stereocilia damage, which was alleviated by APG overexpression. This study highlights the potential of regulating multiple transcription factors to promote vestibular HC regeneration.
毛细胞（HCs）对于前庭功能至关重要，哺乳动物前庭毛细胞的不可逆损伤与眩晕密切相关。通过外源基因传递刺激毛细胞再生是恢复前庭功能的理想治疗方法。Atoh1、Pou4f3和Gfi1（统称为APG）的过表达已证明在促进耳蜗毛细胞再生方面具有疗效。然而，APG对前庭毛细胞再生的影响仍不清楚。在这里，我们使用腺相关病毒内耳（AAVie）作为载体，将APG递送至新生小鼠的椭圆囊，并通过免疫荧光染色评估毛细胞和支持细胞（SCs）的形态和数量。使用GLAST;Rosa26小鼠品系追踪支持细胞。结果表明，APG过表达导致新生小鼠椭圆囊中大量支持细胞转分化为毛细胞。此外，APG过表达通过促进支持细胞增殖来维持支持细胞数量。持续的Atoh1过表达会导致静纤毛损伤，而APG过表达可减轻这种损伤。这项研究突出了调节多种转录因子以促进前庭毛细胞再生的潜力。
