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Updated: Jul 11, 2025

Initiating Differentiation in Immortalized Multipotent Otic Progenitor Cells
Published on: January 2, 2016
The proper timing of Atoh1 expression is pivotal for hair cell subtype differentiation and the establishment of inner
Dan You1,2, Wenli Ni1,2, Yikang Huang1,2
1ENT Institute, Department of Otorhinolaryngology, Eye and ENT Hospital, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, The Institutes of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200031, People's Republic of China.
Abstract:
Atoh1 overexpression is essential for hair cell (HC) regeneration in the sensory epithelium of mammalian auditory and vestibular organs. However, Atoh1 overexpression alone cannot induce fully mature and functional HCs in the mammalian inner ear. In the current study, we investigated the effect of Atoh1 constitutive overexpression in native HCs by manipulating Atoh1 expression at different developmental stages. We demonstrated that constitutive overexpression of Atoh1 in native vestibular HCs did not affect cell survival but did impair vestibular function by interfering with the subtype differentiation of HCs and hair bundle development. In contrast, Atoh1 overexpression in cochlear HCs impeded their maturation, eventually leading to gradual HC loss in the cochlea and hearing dysfunction. Our study suggests that time-restricted Atoh1 expression is essential for the differentiation and survival of HCs in the inner ear, and this is pivotal for both hearing and vestibular function re-establishment through Atoh1 overexpression-induced HC regeneration strategies.
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