The chromatin remodelling factor Chd7 protects auditory neurons and sensory hair cells from stress-induced degeneration.
The chromatin remodelling factor Chd7 protects auditory neurons and sensory hair cells from stress-induced degeneration.
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DOI：
10.1038/s42003-021-02788-6
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发表时间：
2021-11-03
影响因子：
5.9
通讯作者：
Streit A
中科院分区：
文献类型：
--
作者：
Ahmed M;Moon R;Prajapati RS;James E;Basson MA;Streit A
神经元和感觉细胞特别容易受到氧化应激的影响，这是由于它们在刺激感知和传递过程中的高需氧量。保护它们免受压力诱导的死亡和退化的机制仍然难以捉摸。在这里，我们表明，胚胎缺失的染色体结构域解旋酶DNA结合蛋白7（CHD 7）在听觉神经元或毛细胞导致感音神经性听力损失由于出生后退化的两种细胞类型。从机制上讲，我们证明CHD 7控制主要应激途径组分的表达。在缺乏这种物质的情况下，毛细胞是高度敏感的，在短暂暴露于应激诱导物后迅速死亡，这表明听力开始时的声音引发了它们的退化。在人类中，CHD 7单倍不足导致CHARGE综合征，这是一种影响包括耳朵在内的多个器官的疾病。我们的研究结果表明，CHD 7突变导致发育沉默表型，使细胞易于因保护机制失效而发生出生后退化。为了提高我们对保护耳毛细胞免受应激诱导死亡的机制的理解，Ahmed等人删除了小鼠听觉神经元和毛细胞中的染色体结构域解旋酶DNA结合蛋白7（chromodomain helicase DNA-binding protein 7，CHD 7）。他们观察到感音神经性听力损失，并证明CHD 7控制应激通路成分的表达，这可能有助于解释CHD 7单倍不足如何导致与CHARGE综合征相关的耳部变化。
Neurons and sensory cells are particularly vulnerable to oxidative stress due to their high oxygen demand during stimulus perception and transmission. The mechanisms that protect them from stress-induced death and degeneration remain elusive. Here we show that embryonic deletion of the chromodomain helicase DNA-binding protein 7 (CHD7) in auditory neurons or hair cells leads to sensorineural hearing loss due to postnatal degeneration of both cell types. Mechanistically, we demonstrate that CHD7 controls the expression of major stress pathway components. In its absence, hair cells are hypersensitive, dying rapidly after brief exposure to stress inducers, suggesting that sound at the onset of hearing triggers their degeneration. In humans, CHD7 haploinsufficiency causes CHARGE syndrome, a disorder affecting multiple organs including the ear. Our findings suggest that CHD7 mutations cause developmentally silent phenotypes that predispose cells to postnatal degeneration due to a failure of protective mechanisms. To improve our understanding of the mechanisms that protect hair cells in the ear from stress-induced death, Ahmed et al delete the chromodomain helicase DNA-binding protein 7 (CHD7) in auditory neurons and hair cells in mice. They observe sensorineural hearing loss and demonstrate that CHD7 controls the expression of stress pathway components, which could help to explain how CHD7 haploinsufficiency causes changes in the ear associated with CHARGE syndrome.
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影响因子：
11.8
作者：
Ahmed, Mohi;Wong, Elaine Y. M.;Sun, Jianbo;Xu, Jinshu;Wang, Feng;Xu, Pin-Xian
通讯作者：
Xu, Pin-Xian
影响因子：
3.5
作者：
Bosman, EA;Penn, AC;Steel, KP
通讯作者：
Steel, KP
影响因子：
3.4
作者：
Beurg, Maryline;Nam, Jong-Hoon;Fettiplace, Robert
通讯作者：
Fettiplace, Robert
影响因子：
16.2
作者：
Dallos, Peter;Wu, Xudong;Zuo, Jian
通讯作者：
Zuo, Jian
影响因子：
4.6
作者：
Hansen, Jason M.;Jacob, Benjamin R.;Piorczynski, Ted B.
通讯作者：
Piorczynski, Ted B.