Wang Man, Han Yuechen, An Weibin, Wang Xue, Chen Fang, Lu Junze, Meng Yu, Li Yan, Wang Yanqing, Li Jingxin, Zhao Chunjie, Chai Renjie, Wang Haibo, Liu Wenwen, Xu Lei
Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, 250022, China.
Shandong Institute of Otorhinolaryngology, Jinan, 250022, China.
Cell Commun Signal. 2025 Jan 27;23(1):50. doi: 10.1186/s12964-025-02039-9.
Degeneration of cochlear spiral ganglion neurons (SGNs) leads to irreversible sensorineural hearing loss (SNHL), as SGNs lack regenerative capacity. Although cochlear glial cells (GCs) have some neuronal differentiation potential, their specific identities remain unclear. This study identifies a distinct subpopulation, Frizzled10 positive (FZD10+) cells, as an important type of GC responsible for neuronal differentiation in mouse cochlea. FZD10 + cells can differentiate into various SGN subtypes in vivo, adhering to natural proportions. Wnt signaling enhances the ability of FZD10 + cells to function as neural progenitors and increases the neuronal excitability of the FZD10-derived neurons. Single-cell RNA sequencing analysis characterizes FZD10-derived differentiating cell populations, while crosstalk network analysis identifies multiple signaling pathways and target genes influenced by Wnt signaling that contribute to the function of FZD10 + cells as neural progenitors. Pseudotime analysis maps the differentiation trajectory from proliferated GCs to differentiating neurons. Further experiments indicate that glypican 6 (GPC6) may regulate this neuronal lineage, while GPC6 deficiency diminishes the effects of Wnt signaling on FZD10-derived neuronal differentiation and synapse formation. These findings suggest the critical role of Wnt signaling in the neuronal differentiation derived from cochlear FZD10 + cells and provide insights into the mechanisms potentially involved in this process.
耳蜗螺旋神经节神经元（SGNs）的退化会导致不可逆的感音神经性听力损失（SNHL），因为SGNs缺乏再生能力。尽管耳蜗神经胶质细胞（GCs）具有一定的神经元分化潜能，但其具体特性仍不清楚。本研究确定了一个独特的亚群，即卷曲蛋白10阳性（FZD10+）细胞，作为小鼠耳蜗中负责神经元分化的一种重要类型的GC。FZD10+细胞在体内可分化为各种SGN亚型，并保持自然比例。Wnt信号增强了FZD10+细胞作为神经祖细胞的功能能力，并增加了FZD10衍生神经元的神经元兴奋性。单细胞RNA测序分析对FZD10衍生的分化细胞群体进行了表征，而串扰网络分析确定了受Wnt信号影响的多个信号通路和靶基因，这些通路和基因有助于FZD10+细胞作为神经祖细胞的功能。伪时间分析描绘了从增殖的GCs到分化神经元的分化轨迹。进一步的实验表明，磷脂酰肌醇蛋白聚糖6（GPC6）可能调节这一神经元谱系，而GPC6的缺乏会减弱Wnt信号对FZD10衍生的神经元分化和突触形成的影响。这些发现表明Wnt信号在耳蜗FZD10+细胞衍生的神经元分化中起关键作用，并为这一过程中可能涉及的机制提供了见解。
