REST 维持胚胎干细胞的自我更新和多能性
Sanjay K Singh1, Mohamedi N Kagalwala, Jan Parker-Thornburg
1Department of Cancer Genetics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Nature
|March 26, 2008
概括
神经抑制剂REST通过抑制microRNA-21来维持小鼠胚胎干细胞的自我更新和多能性. 失去REST会导致差异化,而增加REST会促进自我更新和关键的多能性因素.
科学领域:
- 干细胞生物学 干细胞生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 鼠标胚胎干细胞 (ESC) 表达高水平的神经抑制剂REST (RE1沉默转录因子).
- 在社会经济委员会自我更新和多能性中,REST的确切功能仍然不完全理解.
研究的目的:
- 阐明REST在维持小鼠ESC的自我更新和多能性的作用.
- 调查REST影响ESC命运决策的监管机制.
主要方法:
- 分析自我更新中的REST表达水平与区分ESC (胚胎体) 的分析.
- 在小鼠ESC和胚胎体中对REST水平的遗传操纵 (异胞性删除,siRNA敲除,外源性添加).
- 评估自我更新标记物 (Oct4,Nanog,Sox2,c-Myc) 和特定于血统的标记物.
- 染色体免疫沉用于识别miRNA基因上的REST结合位.
- 量化miRNA表达的量化,特别是miR-21.
主要成果:
- 与差异化胚胎体相比,在自我更新的ESC中,REST表达显著更高.
- 在ESC中丧失REST功能导致自我更新的丧失和多个谱系标记的诱导.
- 外源REST的添加挽救了分化细胞的自我更新,并保持了多能性标记.
- REST直接与miRNAs的染色质结合,包括miR-21,这些染色体向自我更新调节器.
- miR-21通过降低Oct4,Nanog,Sox2和c-Myc的调节来抑制ESC自我更新.
结论:
- 休息是维持小鼠ESC自我更新和多能性的关键因素.
- 部分通过抑制miR-21发挥其功能,miR-21是多能性基因的关键负调节器.
- REST是管理ESC命运的监管网络的一个组成部分.
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