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作 者:何才蓉 杨影 黄金炜 陈凤娇 陆莹 丁洁 He Cairong;Yang Ying;Huang Jinwei;Chen Fengjiao;Lu Ying;Ding Jie(Key laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region(Ministry of Educa-tion),College of Life Sciences/Institute of Agro-bioengineering,Guizhou University,Guiyang 550025,China;Guizhou Provincial People's Hospital,Guiyang 550002,China;Department of Anatomy,Basic Medical College,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)
机构地区:[1]贵州大学生命科学学院/农业生物工程研究院,山地植物资源保护与种质创新教育部重点实验室,贵州贵阳550025 [2]贵州省人民医院,贵州贵阳550002 [3]贵州中医药大学基础医学院解剖学教研室,贵州贵阳550025
出 处:《中国病理生理杂志》2023年第9期1666-1674,共9页Chinese Journal of Pathophysiology
基 金:国家自然科学基金资助项目(No.32260163,No.81960838);贵州省科技计划项目(黔科合基础⁃ZK[2021]一般108);贵州省高层次创新人才(黔科合平台人才-GCC[2022]027-1)。
摘 要:听力损失是导致语言障碍和影响人口素质的一种世界性顽疾,主要由内耳毛细胞不可逆损伤所致。治疗此类顽疾的核心是毛细胞再生。直接重编程作为一种细胞再生技术,无需经过多能性细胞阶段便可将一种终末分化细胞直接转变为其他类型的功能细胞或祖细胞,因此也称为谱系重编程[1-2],包括直接和间接两种方式。直接的方式是通过导入谱系特异性转录因子诱导一种类型终末分化细胞转化为另一种细胞类型,如慢病毒载体携带转录因子编码基因感染支持细胞或成纤维细胞,经细胞形态、相关基因和蛋白表达等参数验证获得与正常内耳毛细胞相似的细胞,从而实现毛细胞再生的目的[3-5]。Hair cell regeneration and functional remodeling is an effective method of treating sensorineural deaf-ness.In recent years,direct reprogramming techniques have made substantial progress in the field of hair cell regeneration.Atoh1 is an essential gene that is involved in hair cell morphology and maturation.POU domain class 4 transcription factor 3(Pou4f3)plays a crucial role in the development of all hair cells within the sensory epithelium.Growth factor indepondent-1(Gfi1)is an important transcription factor that is required for hair cell development and survival.Studies have demonstrated that the synergistic regulation of Atoh1,Pou4f3 and Gfi1 promotes hair cell differentiation,as well as functional maturation,in vitro.However,the regulatory mechanisms of these three factors in the development,maturation,and establishment of the auditory function of hair cells are still to be further explored.The aim of this paper is to elucidate the function and mechanis-tic relationship between Atoh1,Pou4f3 and Gfi1 in the functional remodeling of hair cells,as well as to determine the feasi-bility of using the Atoh1-Pou4f3-Gfi1 direct reprogramming strategy in order to restore human hearing in the future.
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