Ototoxicity-induced c-Fos activation underlies the regenerative capacity of the vestibular sensory epithelia
Brief intro:
- Author: Yunzhong Zhang, Dan You, Chenhao Che, Xinyuan Wang, Huawei Li, Yi-Quan Tang, Shan Sun
- Journal: Cell Communication and Signaling
- Doi: https://www.doi.org/10.1186/s12964-025-02446-y
- Publication Date: 2025/10/8
Abstract
The mammalian inner ear exhibits a striking dichotomy in regenerative capacity: while vestibular hair cells retain limited ability to regenerate, cochlear hair cells permanently lose this potential after birth. Exploiting this disparity, we employed single-cell comparative transcriptomics combined with lineage tracing to identify c-Fos as a critical early responder selectively activated in the vestibular epithelium following ototoxic injury. Transcriptomic and chromatin profiling revealed that c-Fos initiates regenerative reprogramming by transcriptionally priming Atoh1, the master regulator of hair cell fate, while synergizing with the Wnt and Notch pathways to balance progenitor proliferation and trans-differentiation. Functional validation showed that c-Fos overexpression significantly promoted vestibular hair cell regeneration and restored balance function in adult mice. Our findings establish c-Fos as a molecular switch bridging acute injury responses to tissue repair and highlight its potential as a therapeutic target for vestibular rehabilitation.
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