Transcriptomic characterization of dying hair cells in the avian cochlea

Transcriptomic characterization of dying hair cells in the avian cochlea
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DOI:
10.1016/j.celrep.2021.108902
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发表时间:
2021-03-23
期刊:
影响因子:
8.8
通讯作者:
Heller,Stefan
Heller,Stefan
中科院分区:
生物学1区
文献类型:
--
作者:
Benkafadar,Nesrine;Janesick,Amanda;Heller,Stefan

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感觉毛细胞容易因包括氨基糖苷类抗生素在内的各种药物引起细胞凋亡。在哺乳动物中,这种脆弱性会导致永久性听力损失,因为丢失的毛细胞无法再生。相反,鸟类的毛细胞会再生,使鸟类内耳成为研究耳毒性和再生的精美模型。在这里,我们对氨基糖苷类处理后的对照毛细胞和垂死毛细胞进行单细胞 RNA 测序和轨迹分析。有趣的是,鸟类耳蜗毛细胞的两种主要亚型(高毛细胞和短毛细胞)的反应不同。与高毛细胞相比,垂死的短毛细胞显示出更多明显的瞬时上调基因。确定的最突出的基因组与钾离子电导相关,表明存在明显的生理差异。此外,在高和短鸟类毛细胞凋亡过程中表达的超过 15,000 个基因的动态特征为进一步研究哺乳动物毛细胞保护和毛细胞再生提供了资源。
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 haircells, tall and shorthair 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.