通过重新编程PTB调节的microRNA电路,直接将纤维细胞转化为神经元
Yuanchao Xue1, Kunfu Ouyang, Jie Huang
1State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China.
Cell
|January 15, 2013
概括
抑制聚皮里米丁通路结合 (PTB) 蛋白,这是大脑发育的关键因素,可以将纤维细胞重编程为功能神经元. 这个过程涉及PTB.
科学领域:
- 分子生物学分子生物学
- 发育神经科学的发展神经科学.
- 细胞重编程 细胞重编程
背景情况:
- 细胞类型转换,包括诱导的多能性和转基因差异化,通常是使用谱系特异的转录因子实现的.
- 聚皮里米丁通路结合 (PTB) 蛋白质在正常大脑发育中起作用,部分是通过与microRNAs的相互作用.
研究的目的:
- 调查抑制PTB蛋白是否可以诱导纤维细胞转分化为功能神经元.
- 阐明PTB调节微RNA功能超出其已知的拼接作用的新型机制.
主要方法:
- 在纤维细胞中对PTB蛋白水平的实验操纵.
- 分析微RNA的向和功能.
- 评估神经元基因表达和细胞表型.
主要成果:
- 仅仅抑制PTB蛋白就足以将纤维细胞转分为功能神经元.
- PTB蛋白通过竞争性地与向mRNA结合并改变RNA二次结构来调节microRNA功能.
- 缓解 PTB 介导的 REST 复合物的抑制,缓解神经元基因,包括 miR-124 和转录因子,促进神经元谱系转换.
结论:
- PTB蛋白作为microRNA活动的关键抑制剂,其抑制是神经元诱导的关键事件.
- 这项研究揭示了PTB在调节microRNA向中的新功能,并为细胞重编程进入神经元提供了一个新的机制.
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