Direct reprogramming of fibroblasts into spiral ganglion neurons by defined transcription factors.

IF 5.9 1区 生物学 Q2 CELL BIOLOGY
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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引用次数: 0

Abstract

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.

通过定义转录因子将成纤维细胞直接重编程为螺旋神经节神经元。
人工耳蜗螺旋神经节神经元(SGNs)的退化是感音神经性听力损失的主要原因之一,并对人工耳蜗植入术的效果产生重大影响。螺旋神经节神经元的功能再生为治疗感音神经性听力损失带来了巨大希望。在这项研究中,我们系统地筛选了 33 个与神经元和 SGN 命运相关的转录调节因子。通过基因表达阵列和主成分分析,我们确定了Ascl1、Pou4f1和Myt1l(APM)在促进SGN功能重编程中的顺序组合。APM 诱导的神经元表达成熟的神经元和 SGN 系特异性标记,显示成熟的 SGN 类电生理特征,并表现出与内源性 SGN 相似的单细胞转录组。因此,转录因子 APM 可作为直接重编程 SGN 和 SGN 损伤听力恢复的新候选因子。
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来源期刊
Cell Proliferation
Cell Proliferation 生物-细胞生物学
CiteScore
14.80
自引率
2.40%
发文量
198
审稿时长
1 months
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.
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