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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。

Single-cell transcriptome analysis reveals three sequential phases of gene expression during zebrafish sensory hair cell regeneration.

机构信息

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.

出版信息

Dev Cell. 2022 Mar 28;57(6):799-819.e6. doi: 10.1016/j.devcel.2022.03.001. Epub 2022 Mar 21.


DOI:10.1016/j.devcel.2022.03.001
PMID:35316618
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9188816/
Abstract

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.

摘要

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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引用本文的文献

[1]
prdm1a drives a fate switch between hair cells of different mechanosensory organs.

Nat Commun. 2025-8-18

[2]
Axonal defasciculation is restricted to specific branching points during regeneration of the lateral line nerve in zebrafish.

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[3]
Stem and progenitor cell proliferation are independently regulated by cell type-specific cyclinD genes.

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[4]
Tnfrsf10 Signaling is Required to Maintain the Stem Cell Niche in the Zebrafish Lateral Line.

bioRxiv. 2025-4-19

[5]
drives a fate switch between hair cells of different mechanosensory organs.

bioRxiv. 2025-6-3

[6]
Optimizing gRNA selection for high-penetrance F0 CRISPR screening for interrogating disease gene function.

Nucleic Acids Res. 2025-2-27

[7]
Complexes of vertebrate TMC1/2 and CIB2/3 proteins form hair-cell mechanotransduction cation channels.

Elife. 2025-1-8

[8]
Long-range enhancers maintain competency for hair cell regeneration in the inner ear.

Proc Natl Acad Sci U S A. 2024-12-17

[9]
New application of ombuoside in protecting auditory cells from cisplatin-induced ototoxicity via the apoptosis pathway.

Heliyon. 2024-10-9

[10]
Stem and progenitor cell proliferation are independently regulated by cell type-specific genes.

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本文引用的文献

[1]
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Innovation (Camb). 2021-7-1

[2]
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Nat Methods. 2021-8

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Adaptive cell invasion maintains lateral line organ homeostasis in response to environmental changes.

Dev Cell. 2021-5-3

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Transcription Factor Reprogramming in the Inner Ear: Turning on Cell Fate Switches to Regenerate Sensory Hair Cells.

Front Cell Neurosci. 2021-3-29

[5]
Combinatorial Atoh1 and Gfi1 induction enhances hair cell regeneration in the adult cochlea.

Sci Rep. 2020-12-8

[6]
Gene regulatory networks controlling vertebrate retinal regeneration.

Science. 2020-11-20

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Changes in regeneration-responsive enhancers shape regenerative capacities in vertebrates.

Science. 2020-9-4

[8]
Characterization of the development of the mouse cochlear epithelium at the single cell level.

Nat Commun. 2020-5-13

[9]
Yap-lin28a axis targets let7-Wnt pathway to restore progenitors for initiating regeneration.

Elife. 2020-4-30

[10]
Ribosome heterogeneity in stem cells and development.

J Cell Biol. 2020-6-1

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