Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell Rep. 2021 Mar 23;34(12):108902. doi: 10.1016/j.celrep.2021.108902.
Sensory hair cells are prone to apoptosis caused by various drugs including aminoglycoside antibiotics. In mammals, this vulnerability results in permanent hearing loss because lost hair cells are not regenerated. Conversely, hair cells regenerate in birds, making the avian inner ear an exquisite model for studying ototoxicity and regeneration. Here, we use single-cell RNA sequencing and trajectory analysis on control and dying hair cells after aminoglycoside treatment. Interestingly, the two major subtypes of avian cochlear hair cells, tall and short hair cells, respond differently. Dying short hair cells show a noticeable transient upregulation of many more genes than tall hair cells. The most prominent gene group identified is associated with potassium ion conductances, suggesting distinct physiological differences. Moreover, the dynamic characterization of >15,000 genes expressed in tall and short avian hair cells during their apoptotic demise comprises a resource for further investigations toward mammalian hair cell protection and hair cell regeneration.
感觉毛细胞容易凋亡由各种药物引起的，包括氨基糖苷类抗生素。在哺乳动物中，这种脆弱性导致永久性听力损失，因为失去的毛细胞不会再生。相反，鸟类的毛细胞会再生，使禽类内耳成为研究耳毒性和再生的理想模型。在这里，我们在氨基糖苷类药物处理后对控制和死亡的毛细胞进行单细胞 RNA 测序和轨迹分析。有趣的是，两种主要类型的禽类耳蜗毛细胞，高和短毛细胞，反应不同。死亡的短毛细胞表现出明显的瞬时上调，比长毛细胞更多的基因。确定的最突出的基因组与钾离子电导有关，表明存在明显的生理差异。此外，在高大和短的禽类毛细胞凋亡过程中表达的>15000 个基因的动态特征构成了进一步研究哺乳动物毛细胞保护和毛细胞再生的资源。
