Casz1对于内毛细胞命运的稳定和外毛细胞的存活均是必需的。

Casz1 is required for both inner hair cell fate stabilization and outer hair cell survival.

作者信息

Sun Yuwei, Ren Minhui, Zhang Yu, Li Shuting, Luo Zhengnan, Sun Suhong, He Shunji, Wang Guangqin, Zhang Di, Mansour Suzanne L, Song Lei, Liu Zhiyong

机构信息

Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.

University of Chinese Academy of Sciences, Beijing, China.

出版信息

Science. 2025 Apr 18;388(6744):eado4930. doi: 10.1126/science.ado4930.

DOI:10.1126/science.ado4930

PMID:39883789

Abstract

Cochlear inner hair cells (IHCs) and outer hair cells (OHCs) require different transcription factors for their cell fate stabilization and survival, which suggests that separate mechanisms are involved. In this study, we found that the transcription factor Casz1 is crucial for early IHC fate consolidation and for OHC survival during mouse development. Loss of Casz1 resulted in transdifferentiation of IHCs into OHCs, without affecting OHC production. However, long-term OHC survival was compromised in mutant mice. In addition, the transcription factor Gata3 was down-regulated in -deleted IHCs, and overexpressing Gata3 partially rescued IHC properties, OHC numbers, and hearing in -deleted mice. Thus, Casz1 plays critical roles in early IHC fate stabilization and OHC survival and could potentially provide a lead for therapies aimed at regenerating both IHCs and OHCs.

摘要

耳蜗内毛细胞（IHCs）和外毛细胞（OHCs）在细胞命运稳定和存活方面需要不同的转录因子，这表明涉及不同的机制。在本研究中，我们发现转录因子Casz1对小鼠发育过程中早期IHC命运巩固和OHC存活至关重要。Casz1的缺失导致IHCs转分化为OHCs，而不影响OHC的产生。然而，突变小鼠的OHC长期存活受到损害。此外，转录因子Gata3在Casz1缺失的IHCs中下调，过表达Gata3可部分挽救Casz1缺失小鼠的IHC特性、OHC数量和听力。因此，Casz1在早期IHC命运稳定和OHC存活中起关键作用，并可能为旨在再生IHCs和OHCs的治疗提供线索。