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作 者:Zhenghong Bi Xiang Li Minhui Ren Yunpeng Gu Tong Zhu Shuting Li Guangqin Wang Suhong Sun Yuwei Sun Zhiyong Liu
机构地区:[1]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 [2]University of Chinese Academy of Sciences,Sciences,Beijing 100049,China [3]Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology,Shanghai 201210,China
出 处:《National Science Review》2022年第12期129-142,共14页国家科学评论(英文版)
基 金:supported by the National Key Research and Development Program of China(2021YFA1101804);the National Natural Science Foundation of China(82000985 and 82101217);the Strategic Priority Research Program of Chinese Academy of Sciences(XDB32060100);the Shanghai Municipal Science and Technology Major Project(2018SHZDZX05);the Innovative Research Team of High-Level Local Universities in Shanghai(SSMU-ZLCX20180601).
摘 要:Atohl is essential for the development of both outer hair cells(OHCs)and inner hair cells(IHCs)in the mammalian co chlea.Whereas Ikzf2 is necessary for OHC development,the key gene re quired 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 Ikzf2.More importantly,persistent expression of Tbx2 coupled with transient Atohl expression effe ctively 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 Atohl in supporting cells represents a new approach for treating deafness related to IHC degeneration.
关 键 词:TBX2 COCHLEA inner hair cell supporting cell Ikzf2 outer hair cell
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