Ototoxicity-induced c-Fos activation underlies the regenerative capacity of the vestibular sensory epithelia.

Yunzhong Zhang, Dan You, Chenhao Che, Xinyuan Wang, Huawei Li, Yi-Quan Tang, Shan Sun

Abstract read

In one paragraph

Article in Cell communication and signaling : CCS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Yunzhong ZhangENT Institute and Otorhinolaryngology, Department of Affiliated Eye and ENT Hospital, Key Laboratory of Hearing Medicine of NHFPC, Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200031, China.

Dan YouENT Institute and Otorhinolaryngology, Department of Affiliated Eye and ENT Hospital, Key Laboratory of Hearing Medicine of NHFPC, Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200031, China.

Chenhao CheENT Institute and Otorhinolaryngology, Department of Affiliated Eye and ENT Hospital, Key Laboratory of Hearing Medicine of NHFPC, Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200031, China.

Xinyuan WangENT Institute and Otorhinolaryngology, Department of Affiliated Eye and ENT Hospital, Key Laboratory of Hearing Medicine of NHFPC, Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200031, China.

Huawei LiENT Institute and Otorhinolaryngology, Department of Affiliated Eye and ENT Hospital, Key Laboratory of Hearing Medicine of NHFPC, Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200031, China. hwli@shmu.edu.cn.

Yi-Quan TangENT Institute and Otorhinolaryngology, Department of Affiliated Eye and ENT Hospital, Key Laboratory of Hearing Medicine of NHFPC, Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200031, China. yqtang@fudan.edu.cn.

Shan SunENT Institute and Otorhinolaryngology, Department of Affiliated Eye and ENT Hospital, Key Laboratory of Hearing Medicine of NHFPC, Shanghai Key Laboratory of Gene Editing and Cell Therapy for Rare Diseases, State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, 200031, China. Shansun@fudan.edu.cn.

Funding

Dream Project of Ministry of Science and Technology of the People's Republic of China 2024YFC2511100/2024YFC2511104National Key Research and Development Program of China 2023YFC2508000National Natural Science Foundation of China 82371146, 82192862National Natural Science Foundation of China 82521001National Natural Science Foundation of China, China 32170694Shanghai Municipal Health Commission 2022XD059Shanghai Municipal Science and Technology Major Project 2018SHZDZX01

6 · The paper itself

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.

Indexed as

Hair Cells, VestibularOtotoxicityProto-Oncogene Proteins c-fosRegenerationAnimalsBasic Helix-Loop-Helix ProteinsCell ProliferationEpitheliumMiceReceptors, NotchAtoh1 protein, mouseBasic Helix-Loop-Helix ProteinsProto-Oncogene Proteins c-fosReceptors, NotchAP-1 transcription factorAtoh1c-FosHair cell regenerationInner earNotch signalingVestibular functionWnt signaling

Identifiers

PMID41063275

DOI10.1186/s12964-025-02446-y

PMCPMC12506291

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LicenceCC BY

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.