Yuhang Huang, Zhen Chen, Jiang Chen, Jingyue Liu, Cui Qiu, Qing Liu, Linqing Zhang, Guang-Jie Zhu, Xiaofeng Ma, Shuohao Sun, Yun Stone Shi, Guoqiang Wan
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Direct reprogramming of fibroblasts into spiral ganglion neurons by defined transcription factors.
Degeneration of the cochlear spiral ganglion neurons (SGNs) is one of the major causes of sensorineural hearing loss and significantly impacts the outcomes of cochlear implantation. Functional regeneration of SGNs holds great promise for treating sensorineural hearing loss. In this study, we systematically screened 33 transcriptional regulators implicated in neuronal and SGN fate. Using gene expression array and principal component analyses, we identified a sequential combination of Ascl1, Pou4f1 and Myt1l (APM) in promoting functional reprogramming of SGNs. The neurons induced by APM expressed mature neuronal and SGN lineage-specific markers, displayed mature SGN-like electrophysiological characteristics and exhibited single-cell transcriptomes resembling the endogenous SGNs. Thus, transcription factors APM may serve as novel candidates for direct reprogramming of SGNs and hearing recovery due to SGN damages.
期刊介绍:
Cell Proliferation
Focus:
Devoted to studies into all aspects of cell proliferation and differentiation.
Covers normal and abnormal states.
Explores control systems and mechanisms at various levels: inter- and intracellular, molecular, and genetic.
Investigates modification by and interactions with chemical and physical agents.
Includes mathematical modeling and the development of new techniques.
Publication Content:
Original research papers
Invited review articles
Book reviews
Letters commenting on previously published papers and/or topics of general interest
By organizing the information in this manner, readers can quickly grasp the scope, focus, and publication content of Cell Proliferation.