发育以及向内毛细胞的转分化需要Tbx2。
Development and transdifferentiation into inner hair cells require Tbx2.
作者信息
Bi Zhenghong, Li Xiang, Ren Minhui, Gu Yunpeng, Zhu Tong, Li Shuting, Wang Guangqin, Sun Suhong, Sun Yuwei, Liu Zhiyong
机构信息
Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
出版信息
Natl Sci Rev. 2022 Aug 9;9(12):nwac156. doi: 10.1093/nsr/nwac156. eCollection 2022 Dec.
Atoh1 is essential for the development of both outer hair cells (OHCs) and inner hair cells (IHCs) in the mammalian cochlea. Whereas is necessary for OHC development, the key gene required for IHC development remains unknown. We found that deletion of Tbx2 in neonatal IHCs led to their transdifferentiation into OHCs by repressing 26.7% of IHC genes and inducing 56.3% of OHC genes, including . More importantly, persistent expression of Tbx2 coupled with transient Atoh1 expression effectively reprogrammed non-sensory supporting cells into new IHCs expressing the functional IHC marker vGlut3. The differentiation status of these new IHCs was considerably more advanced than that previously reported. Thus, Tbx2 is essential for IHC development and co-upregulation of Tbx2 with Atoh1 in supporting cells represents a new approach for treating deafness related to IHC degeneration.
Atoh1对于哺乳动物耳蜗中外毛细胞（OHC）和内毛细胞（IHC）的发育至关重要。虽然[此处原文缺失相关基因名称]对于OHC发育是必需的，但IHC发育所需的关键基因仍然未知。我们发现，新生IHC中Tbx2的缺失通过抑制26.7%的IHC基因并诱导56.3%的OHC基因（包括[此处原文缺失相关基因名称]），导致它们转分化为OHC。更重要的是，Tbx2的持续表达与短暂的Atoh1表达相结合，有效地将非感觉支持细胞重编程为表达功能性IHC标记物vGlut3的新IHC。这些新IHC的分化状态比先前报道的要先进得多。因此，Tbx2对于IHC发育至关重要，并且在支持细胞中Tbx2与Atoh1的共同上调代表了一种治疗与IHC退化相关耳聋的新方法。
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