Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma.
Notch inhibition induces cochlear hair cell regeneration and recovery of hearing after acoustic trauma.
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DOI：
10.1016/j.neuron.2012.10.032
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发表时间：
2013-01-09
期刊：
影响因子：
16.2
通讯作者：
Edge AS
中科院分区：
文献类型：
--
作者：
Mizutari K;Fujioka M;Hosoya M;Bramhall N;Okano HJ;Okano H;Edge AS
由于听觉毛细胞受损导致的听力损失通常是不可逆的，因为哺乳动物的毛细胞无法再生。在此，我们表明，当用一种在体外刺激内耳干细胞分化为毛细胞方面具有效力的γ-分泌酶抑制剂抑制Notch信号通路时，可以诱导产生新的毛细胞，并能使噪声损伤的耳朵部分恢复听力。毛细胞的产生是由于Notch信号通路受抑制后，碱性螺旋 - 环 - 螺旋（bHLH）转录因子Atoh1水平升高所致。利用Cre/lox系统对表达Sox2的细胞进行体内前瞻性标记，明确证明毛细胞的产生是由支持细胞转分化而来。因此，通过药物抑制Notch信号通路来调控体内耳蜗感觉细胞的命运是一种治疗耳聋的潜在治疗方法。
Hearing loss due to damage to auditory hair cells is normally irreversible because mammalian hair cells do not regenerate. Here, we show that new hair cells can be induced and can cause partial recovery of hearing in ears damaged by noise trauma, when Notch signaling is inhibited by a γ-secretase inhibitor selected for potency in stimulating hair cell differentiation from inner ear stem cells in vitro. Hair cell generation resulted from an increase in the level of bHLH transcription factor, Atoh1, in response to inhibition of Notch signaling. In vivo prospective labeling of Sox2-expressing cells with a Cre/lox system unambiguously demonstrated that hair cell generation resulted from transdifferentiation of supporting cells. Manipulating cell fate of cochlear sensory cells in vivo by pharmacological inhibition of Notch signaling is thus a potential therapeutic approach to the treatment of deafness.
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影响因子：
5.7
作者：
Edge AS;Chen ZY
通讯作者：
Chen ZY
DOI：
10.1523/jneurosci.3389-10.2011
发表时间：
2011-01-19
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Liberman LD;Wang H;Liberman MC
通讯作者：
Liberman MC
DOI：
10.1523/jneurosci.2057-11.2011
发表时间：
2011-10-26
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Lin V;Golub JS;Nguyen TB;Hume CR;Oesterle EC;Stone JS
通讯作者：
Stone JS
影响因子：
2.5
作者：
Cafaro, Jon;Lee, Gi Soo;Stone, Jennifer S.
通讯作者：
Stone, Jennifer S.
影响因子：
64.8
作者：
Gubbels, Samuel P.;Woessner, David W.;Mitchell, John C.;Ricci, Anthony J.;Brigande, John V.
通讯作者：
Brigande, John V.