PDF(Pubmed)
Abstract：
Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.
摘要：
哺乳动物内耳毛细胞损失导致永久性听力和平衡功能障碍。与耳蜗相比，鼠膜的前庭毛细胞具有一定的再生能力。人腺体毛细胞是否在体内再生仍然未知。我们在这里现场采购，来自器官捐献者和前庭神经鞘瘤患者的成熟细胞，并以前所未有的分辨率呈现一个经过验证的单细胞转录组学图谱。我们描述了13种感觉和非感觉细胞类型的标记，在人和小鼠毛细胞和支持细胞的转录组之间具有部分重叠和相关性。我们进一步发现了毛细胞前体特有的转录组，在前庭神经鞘瘤中出乎意料地增加了14倍，证明了人类正在进行的再生。最后,支持细胞到毛细胞轨迹分析揭示了5种不同的动态基因表达模式和相关途径，包括Wnt和IGF-1信号传导。我们的数据集构成了基础资源，可通过基于Web的界面访问，有助于增进对正常和患病人类内耳的了解。
