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prdm1a驱动不同机械感觉器官毛细胞之间的命运转换。

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

作者信息

Sandler Jeremy E, Tsai Ya-Yin, Chen Shiyuan, Sabin Logan, Lush Mark E, Sur Abhinav, Ellis Elizabeth, Tran Nhung T T, Cook Malcolm, Scott Allison R, Kniss Jonathan S, Farrell Jeffrey A, Piotrowski Tatjana

机构信息

Stowers Institute for Medical Research, Kansas City, MO, USA.

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD, USA.

出版信息

Nat Commun. 2025 Aug 18;16(1):7662. doi: 10.1038/s41467-025-62942-0.


DOI:10.1038/s41467-025-62942-0
PMID:40825768
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12361438/
Abstract

Vertebrate inner ear mechanosensory hair cells detect sound and gravitational forces. Additionally, fishes have homologous lateral line hair cells in the skin that detect water vibrations for orientation and predator avoidance. Hair cells in the lateral line and ear of fishes and other non-mammalian vertebrates regenerate readily after damage, but mammalians lack this ability, causing deafness and vestibular defects. As yet, experimental attempts at hair cell regeneration in mice result in incompletely differentiated and immature hair cells. Despite differences in regeneration capabilities, the gene regulatory networks (GRNs) driving hair cell maturation during development are highly similar across vertebrates. Here, we show that the transcription factor prdm1a plays a key role in the hair cell fate GRN in the zebrafish lateral line. Mutating prdm1a respecifies lateral line hair cells into ear hair cells, altering morphology and transcriptome. Understanding how transcription factors control diverse hair cell fates in zebrafish is crucial for understanding the yet unsolved regeneration of diverse hair cells in mammalian ears to restore hearing and balance.

摘要

脊椎动物的内耳机械感觉毛细胞能检测声音和重力。此外,鱼类在皮肤中有同源的侧线毛细胞,可检测水的振动以进行定向和躲避捕食者。鱼类和其他非哺乳动物脊椎动物的侧线和耳朵中的毛细胞在受损后很容易再生,但哺乳动物缺乏这种能力,这会导致耳聋和前庭缺陷。到目前为止,在小鼠中进行毛细胞再生的实验尝试产生的是未完全分化和不成熟的毛细胞。尽管再生能力存在差异,但在发育过程中驱动毛细胞成熟的基因调控网络(GRN)在整个脊椎动物中高度相似。在这里,我们表明转录因子prdm1a在斑马鱼侧线的毛细胞命运GRN中起关键作用。使prdm1a发生突变会将侧线毛细胞重新指定为耳毛细胞,从而改变形态和转录组。了解转录因子如何控制斑马鱼中不同的毛细胞命运对于理解哺乳动物耳朵中尚未解决的各种毛细胞再生以恢复听力和平衡至关重要。

相似文献

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

Nat Commun. 2025-8-18

[2]
drives a fate switch between hair cells of different mechanosensory organs.

bioRxiv. 2025-6-3

[3]
is required for hair cell development and regeneration in the zebrafish lateral line.

bioRxiv. 2024-4-15

[4]
Anatomical and molecular insights into avian inner ear sensory hair cell regeneration.

Dev Biol. 2025-9

[5]
Mosaic Atoh1 deletion in the chick auditory epithelium reveals a homeostatic mechanism to restore hair cell number.

Dev Biol. 2024-12

[6]
Transcriptomic change in human utricles after aminoglycoside-induced hair cell ablation: Dynamic alterations to hair cell and supporting cell genes.

Hear Res. 2025-6-20

[7]
Atoh1 is required for the formation of lateral line electroreceptors and hair cells, whereas Foxg1 represses an electrosensory fate.

Elife. 2025-6-25

[8]
Single-cell transcriptome analysis reveals three sequential phases of gene expression during zebrafish sensory hair cell regeneration.

Dev Cell. 2022-3-28

[9]
Ear drops for the removal of ear wax.

Cochrane Database Syst Rev. 2018-7-25

[10]
Topical antibiotics with steroids for chronic suppurative otitis media.

Cochrane Database Syst Rev. 2025-6-9

本文引用的文献

[1]
Revisiting the Potency of Tbx2 Expression in Transforming Outer Hair Cells into Inner Hair Cells at Multiple Ages In Vivo.

J Neurosci. 2024-6-5

[2]
Canalizing cell fate by transcriptional repression.

Mol Syst Biol. 2024-3

[3]
Single-cell analysis of shared signatures and transcriptional diversity during zebrafish development.

Dev Cell. 2023-12-18

[4]
Transmembrane Channel-Like (Tmc) Subunits Contribute to Frequency Sensitivity in the Zebrafish Utricle.

J Neurosci. 2024-1-3

[5]
Gene regulatory network inference in the era of single-cell multi-omics.

Nat Rev Genet. 2023-11

[6]
Dictionary learning for integrative, multimodal and scalable single-cell analysis.

Nat Biotechnol. 2024-2

[7]
Epistatic genetic interactions between Insm1 and Ikzf2 during cochlear outer hair cell development.

Cell Rep. 2023-5-30

[8]
Vestibular physiology and function in zebrafish.

Front Cell Dev Biol. 2023-4-18

[9]
Asymmetric mechanotransduction by hair cells of the zebrafish lateral line.

Curr Biol. 2023-4-10

[10]
Single-cell multi-omics and lineage tracing to dissect cell fate decision-making.

Stem Cell Reports. 2023-1-10

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