Single-nucleus profiling of mouse inner ear aging uncovers cell type heterogeneity and hair cell subtype-specific age-related signatures.

IF 6.9 1区生物学 Q1 CELL BIOLOGY

Cell reports Pub Date : 2025-06-24 Epub Date: 2025-05-28 DOI:10.1016/j.celrep.2025.115781

Mingyu Xia, Feng Zhang, Jiaoyao Ma, Yunjie Li, Gaogan Jia, Mingxuan Wu, Yiyun Lou, Yaoqian Liu, Lingjie Li, Huawei Li, Wenyan Li

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Abstract

Degeneration of the auditory and vestibular hair cells (HCs) leads to dysfunction of two essential senses: hearing loss and decompensated balance perception. However, the cellular and molecular mechanisms governing inner ear aging and its link to dysfunctions of sensory HCs remain unclear. Here, we constructed an aging-associated cell atlas of cochlear and utricular tissues in C57BL/6J mice through single-nucleus RNA sequencing, revealing transcriptionally distinct hair cell subtypes and spatially restricted molecular markers that delineate specific cellular populations. We uncovered activation of macrophages and shaped inflamed niches in the aged inner ear. Furthermore, we demonstrated the cell type-specific signatures of aging between the two organs, with focused characterization in six HC subtypes uncovering core mechanisms like dysregulated RNA splicing underlying degeneration. Crucially, suppressing RNA splicing factor Rbm25 abolished inflammation-induced HC deterioration. Our study reveals complex, multifactorial mechanisms that underlie inner ear aging and offer potential targets for preventing HC degeneration.

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小鼠内耳衰老的单核分析揭示了细胞类型异质性和毛细胞亚型特异性年龄相关特征。

听觉和前庭毛细胞（HCs）的退化导致两种基本感觉功能障碍：听力损失和失代偿平衡感知。然而，内耳衰老的细胞和分子机制及其与感觉hc功能障碍的联系尚不清楚。在这里，我们通过单核RNA测序构建了C57BL/6J小鼠耳蜗和脑室组织的衰老相关细胞图谱，揭示了转录不同的毛细胞亚型和空间限制的分子标记，描绘了特定的细胞群体。我们发现了巨噬细胞的活化和老化内耳中形成的炎症壁龛。此外，我们展示了两个器官之间的细胞类型特异性衰老特征，重点表征了六种HC亚型，揭示了核心机制，如退化背后的RNA剪接失调。关键是，抑制RNA剪接因子Rbm25可消除炎症诱导的HC恶化。我们的研究揭示了内耳老化背后复杂的多因素机制，并为预防HC变性提供了潜在的靶点。

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

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.