Co-overexpression of Atoh1, Pou4f3, and Gfi1 enhances the transdifferentiation of supporting cells into hair cells in the neonatal mouse utricle

IF 2.5 4区医学 Q3 NEUROSCIENCES

Neuroscience Letters Pub Date : 2025-01-28 DOI:10.1016/j.neulet.2025.138136

Ming-Yu Hao , Wei Su , Jun-Yi Xu , Zhong-Rui Chen , Lu He , Jing-Ying Guo , Ke Liu , Shu-Sheng Gong , Guo-Peng Wang

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引用次数: 0

Abstract

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^CreERT;Rosa26^tdTomato 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.

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毛细胞对前庭功能至关重要，哺乳动物前庭毛细胞的不可逆损伤与眩晕密切相关。通过外源基因递送刺激毛细胞再生是恢复前庭功能的理想治疗方法。过量表达 Atoh1、Pou4f3 和 Gfi1（统称为 APG）已被证明能有效促进耳蜗中 HC 的再生。然而，APG 对前庭 HC 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送入新生小鼠的耳蜗，并通过免疫荧光染色评估了HCs和支持细胞（SCs）的形态和数量。GLASTCreERT;Rosa26tdTomato小鼠品系用于追踪SCs。结果表明，APG过表达会导致新生小鼠胞器中的SC大量转分化为HC。此外，APG过表达还能促进SC增殖，从而维持SC的数量。持续过表达 Atoh1 会造成立体纤毛损伤，而过表达 APG 则可减轻损伤。这项研究强调了调节多种转录因子促进前庭HC再生的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuroscience Letters 医学-神经科学

CiteScore

5.20

自引率

0.00%

发文量

408

审稿时长

50 days

期刊介绍： Neuroscience Letters is devoted to the rapid publication of short, high-quality papers of interest to the broad community of neuroscientists. Only papers which will make a significant addition to the literature in the field will be published. Papers in all areas of neuroscience - molecular, cellular, developmental, systems, behavioral and cognitive, as well as computational - will be considered for publication. Submission of laboratory investigations that shed light on disease mechanisms is encouraged. Special Issues, edited by Guest Editors to cover new and rapidly-moving areas, will include invited mini-reviews. Occasional mini-reviews in especially timely areas will be considered for publication, without invitation, outside of Special Issues; these un-solicited mini-reviews can be submitted without invitation but must be of very high quality. Clinical studies will also be published if they provide new information about organization or actions of the nervous system, or provide new insights into the neurobiology of disease. NSL does not publish case reports.