Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA.
Dev Cell. 2022 Mar 28;57(6):799-819.e6. doi: 10.1016/j.devcel.2022.03.001. Epub 2022 Mar 21.
Loss of sensory hair cells (HCs) in the mammalian inner ear leads to permanent hearing and vestibular defects, whereas loss of HCs in zebrafish results in their regeneration. We used single-cell RNA sequencing (scRNA-seq) to characterize the transcriptional dynamics of HC regeneration in zebrafish at unprecedented spatiotemporal resolution. We uncovered three sequentially activated modules: first, an injury/inflammatory response and downregulation of progenitor cell maintenance genes within minutes after HC loss; second, the transient activation of regeneration-specific genes; and third, a robust re-activation of developmental gene programs, including HC specification, cell-cycle activation, ribosome biogenesis, and a metabolic switch to oxidative phosphorylation. The results are relevant not only for our understanding of HC regeneration and how we might be able to trigger it in mammals but also for regenerative processes in general. The data are searchable and publicly accessible via a web-based interface.
哺乳动物内耳中感觉毛细胞(HCs)的丧失会导致永久性听力和前庭缺陷,而斑马鱼中 HCs 的丧失会导致其再生。我们使用单细胞 RNA 测序(scRNA-seq)以空前的时空分辨率来描述斑马鱼中 HC 再生的转录动力学。我们揭示了三个依次激活的模块:首先,在 HC 丧失后几分钟内,发生损伤/炎症反应和祖细胞维持基因的下调;其次,短暂激活再生特异性基因;最后,发育基因程序的强烈重新激活,包括 HC 特化、细胞周期激活、核糖体生物发生和氧化磷酸化的代谢转换。这些结果不仅与我们对 HC 再生的理解以及我们如何在哺乳动物中触发它有关,而且与一般的再生过程有关。这些数据可通过基于网络的界面进行搜索和公开访问。
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