单细胞转录组图谱揭示前庭系统中的细胞异质性和器官特异性特征

文献信息

中文摘要

前庭感觉上皮由椭圆囊、球囊和壶腹嵴组成，具有不同的再生能力和生理特化，但支配其发育的细胞异质性和调控逻辑仍不完全清楚。在此，我们构建了出生后第1天小鼠前庭器官的单细胞转录组图谱，鉴定出九个转录上不同的上皮亚群，具有明显的器官特异性分布。轨迹重建揭示了一个保守的三阶段分化级联（Sox2→Atoh1→Myo7a），但拓扑结构存在分歧：壶腹/球囊中为线性祖细胞进展，而椭圆囊中为分支路径。单细胞调控网络推断和聚类分析发现了16个调控子，包括毛细胞中由Pou4f3驱动的程序。Wilcoxon检验还鉴定出Nfib是球囊优势暗细胞前体（出生后第1天Kcne1阴性）中差异表达的转录因子。CellChat分析进一步证明了不同的相互作用组架构：球囊采用高容量可塑性信号（胰岛素样生长因子），壶腹强调细胞外基质重塑（胶原/血小板反应蛋白），而椭圆囊和壶腹共享神经黏附特征（神经元生长调节因子/细胞黏附分子），并在椭圆囊中定量富集。这些发现建立了一个将转录程序与器官特异性通讯策略联系起来的分子框架，为前庭功能多样化和靶向再生策略提供了机制见解。

英文摘要

The vestibular sensory epithelia, comprising the utricle, saccule, and ampullary cristae, exhibit distinct regenerative capacities and physiological specializations, yet the cellular heterogeneity and regulatory logic governing their development remain incompletely understood. Here, we generated a single-cell transcriptomic atlas of postnatal day 1 mouse vestibular organs, identifying nine transcriptionally distinct epithelial subpopulations with marked organ-specific distributions. Trajectory reconstruction revealed a conserved tri-phase differentiation cascade (Sox2→Atoh1→Myo7a) but divergent topologies: linear progenitor progression in ampulla/saccule versus branched paths in utricle. Single-cell regulatory network inference and clustering analysis uncovered 16 regulons, including Pou4f3-driven programs in hair cells. Wilcoxon testing additionally identified Nfib as a differentially expressed transcription factor in saccule-predominant dark-cell precursors (Kcne1-negative at postnatal day 1). CellChat analysis further demonstrated distinct interactomic architectures: the saccule employs high-capacity plastic signaling (insulin-like growth factor), the ampulla emphasizes extracellular matrix remodeling (collagen/thrombospondin), and the utricle and ampulla share neural adhesion signatures (neuronal growth regulator/cell adhesion molecule), with quantitative enrichment in the utricle. These findings establish a molecular framework linking transcriptional programs to organ-specific communication strategies, providing mechanistic insights into vestibular functional diversification and targeted regenerative strategies.