通过bHLH转录因子Tfe3的细胞内再分配,可以从多能性中退出
Joerg Betschinger1, Jennifer Nichols, Sabine Dietmann
1Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge CB2 1QR, UK. jb579@cam.ac.uk
Cell
|April 16, 2013
概括
瘤抑制剂Folliculin (Flcn) 和Tsc2通过调节Tfe3.3来防止胚胎干细胞 (ESC) 的结合. 强制核Tfe3保持多能性,揭示了血统承诺的静电器.
科学领域:
- 干细胞生物学 干细胞生物学
- 多能性的分子机制.
- 细胞命运的决定 细胞命运的决定
背景情况:
- 鼠标胚胎干细胞 (ESC) 的自我更新是众所周知的.
- 控制多能性退出的分子机器仍然定义不佳.
研究的目的:
- 确定调节退出社会经济委员会多能性的因素.
- 阐明Folliculin (Flcn) 和Tsc2在社会经济委员会承诺中的作用.
主要方法:
- 大规模的小干扰RNA (siRNA) 屏幕.
- 分析了哺乳动物对拉巴胺素 (mTOR) 途径的标.
- 研究转录因子Tfe3的局部化和活性.
- 全基因组定位和功能分析.
- 在体内对表皮质细胞发育的研究.
主要成果:
- 淘汰Flcn和Tsc2阻止了ESC的承诺.
- 与Fnip1/2一起的Flcn限制了核Tfe3,促进了分化.
- 强制核 Tfe3 允许 ESC 抵制差异化.
- Tfe3直接调节Esrrb,并集成到多能电路中.
- 在体内发育过程中,Flcn-Fnip1/2会影响Tfe3局部化.
结论:
- Flcn-Tsc2-mTOR通路和Flcn-Fnip1/2-Tfe3轴充当细胞内在的静电器,用于多能性破坏稳定.
- Tfe3 是一个关键的调节器,整合了多能性和差异化.
- 流动介导的Tfe3调节对于表皮质细胞的发育进展至关重要.
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