Single-cell transcriptome analysis reveals three sequential phases of gene expression during zebrafish sensory hair cell regeneration.
Single-cell transcriptome analysis reveals three sequential phases of gene expression during zebrafish sensory hair cell regeneration.
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单细胞转录组分析揭示了斑马鱼感觉毛细胞再生过程中基因表达的三个连续阶段。
DOI：
10.1016/j.devcel.2022.03.001
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发表时间：
2022-03-28
影响因子：
11.8
通讯作者：
Piotrowski, Tatjana
中科院分区：
文献类型：
--
作者：
Baek, Sungmin;Tran, Nhung T. T.;Diaz, Daniel C.;Tsai, Ya-Yin;Acedo, Joaquin Navajas;Lush, Mark E.;Piotrowski, Tatjana
哺乳动物内耳感觉毛细胞（HCs）的缺失会导致永久性听力和前庭功能缺陷，而斑马鱼内耳感觉毛细胞的缺失会导致它们的再生。我们使用scRNA-Seq以前所未有的时空分辨率表征斑马鱼HC再生的转录动力学。我们发现了三个依次激活的模块。首先，在HC丢失后几分钟内出现损伤/炎症反应和祖细胞维持基因的下调。第二，再生特异性基因的瞬时激活。第三，发育基因程序的强大再激活，包括HC规范、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能够在哺乳动物中触发它有关，而且与一般的再生过程有关。这些数据可以通过一个基于网络的界面进行搜索和公开访问。哺乳动物不能再生内耳毛细胞的原因尚不清楚。Baek等人对斑马鱼感觉毛细胞再生过程中的6个时间点进行了scRNASeq分析。再生依赖于三个随后被激活的基因模块，这些基因模块可以作为触发哺乳动物再生的蓝图。
Loss of sensory hair cell (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 scRNA-Seq to characterize the transcriptional dynamics of HC regeneration in zebrafish at unprecedented spatio-temporal 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 reactivation of developmental gene programs, including HC specification, cell cycle activation, ribosome biogenesis, and a metabolic switch to oxidative phosphorylation. The results are not only relevant 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 is searchable and publicly accessible via a web-based interface. It is not understood why mammals cannot regenerate their inner ear hair cells. Baek et al., performed scRNASeq analyses of six time points during sensory hair cell regeneration in zebrafish. Regeneration depends on three, subsequently activated gene modules which can serve as a blueprint to trigger regeneration in mammals.
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