Journal of Shanghai Jiao Tong University (Medical Science) ›› 2026, Vol. 46 ›› Issue (10): 1313-1322.doi: 10.3969/j.issn.1674-8115.2026.10.001

• Innovative research team achievement column •    

Changes in cochlear cell subsets in Otoferlin-knockout deaf mice revealed by single-cell sequencing

Ma Xiaotong1,2,3,4, Cai Ruijie1,2,3,4, Lai Yiyang1,2,3,4, Wang Ziquan1,2,3,4, Liu Huihui1,2,3,4(), Wu Hao1,2,3,4()   

  1. 1.Department of Otorhinolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
    2.Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China
    3.Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai 200125, China
    4.Department of Audiology and Speech-Language Pathology, School of Medical Technology, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China
  • Received:2026-01-20 Accepted:2026-04-22 Online:2026-10-28 Published:2026-10-28
  • Contact: Liu Huihui, Wu Hao E-mail:liuhent9th@163.com;wuhao@shsmu.edu.cn
  • Supported by:
    Shanghai Science and Technology Innovation Action Plan(24J12800300);National Natural Science Foundation of China for Young Scientists(82101211);China Postdoctoral Science Foundation(2024M752052)

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Abstract:

Objective ·To investigate the effects of Otoferlin gene-knockout on transcriptional profiles and cellular homeostasis of different cochlear cell subsets in mice, and to explore its role in the pathogenesis of hereditary deafness. Methods ·Otoferlin-knockout mice (Otof-/- group) and wild-type mice (WT group) with the same genetic background were used. Single-cell RNA sequencing was performed to obtain transcriptional profiles of cochlear cells. Cell-specific marker genes were used to identify cochlear cell subsets. Differentially expressed genes (DEGs) were screened, followed by Gene Ontology (GO) functional enrichment analysis. Immunofluorescence staining, endolymphatic potential (EP) measurement, and morphological assessment of the stria vascularis were applied for functional validation. Proteomics and gene set module scoring were further used to reveal the impacts of Otoferlin knockout on cochlear cells. Results ·A total of 24 cochlear cell subsets were identified via single-cell sequencing. No significant difference was observed in the overall proportions of cell subsets between the two groups, while DEGs exhibited obvious cell-type-specific distribution patterns. DEGs were most enriched in supporting cells, including outer sulcus cells, pillar cells, and Deiters' cells, and were mainly involved in extracellular matrix organization, cochlear development, and ribosome metabolism. DEGs in outer hair cells were significantly enriched in mitochondrial oxidative respiratory chain pathways. In stria vascularis cells, the expression patterns of genes related to ion homeostasis and epithelial development were markedly altered, with abnormal expression of the key ion transport genes Slc12a2 and Kcnj10. Proteomic analysis further revealed marked abnormalities in endoplasmic reticulum-Golgi vesicular transport and mitochondrial translation pathways in the organ of Corti of Otoferlin-knockout mice compared with WT mice, and such abnormalities were most prominent in stria vascularis cells and some glial cells. Conclusion ·Although the overall composition of cochlear cell subsets did not change significantly in deaf mice with Otoferlin-knockout, ion transport dysfunction in the stria vascularis and a marked reduction in EP can be detected. Deaf mice present functional abnormalities in non-neuronal cells, including those of the stria vascularis.

Key words: single-cell RNA sequencing, Otoferlin gene, hereditary hearing loss, cochlear cell

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