Notch Inhibition Induces Cochlear Hair Cell Regeneration and Recovery of Hearing after Acoustic Trauma

被引：294

作者：

Mizutari, Kunio ^{[1
,2
]}

Fujioka, Masato ^{[1
,2
,3
]}

Hosoya, Makoto ^{[3
]}

Bramhall, Naomi ^{[1
,2
,4
]}

Okano, Hirotaka James ^{[3
]}

Okano, Hideyuki ^{[3
]}

Edge, Albert S. B. ^{[1
,2
,4
]}

机构：

[1] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA

[2] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Tillotson Unit, Boston, MA 02114 USA

[3] Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan

[4] Harvard & MIT, Program Speech & Hearing Biosci & Technol, Div Hlth Sci & Technol, Cambridge, MA 02139 USA

来源：

NEURON | 2013年 / 77卷 / 01期

关键词：

MOUSE INNER-EAR; ROUND WINDOW MEMBRANE; STEM-CELLS; RETINOBLASTOMA PROTEIN; PROGENITOR CELLS; IN-VIVO; EXPRESSION; ORGAN; CORTI; FATE;

D O I：

10.1016/j.neuron.2012.10.032

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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 gamma-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.

引用

页码：58 / 69

页数：12

共 53 条

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