将转录因子控制电路重置为人类基本状态多能性
Yasuhiro Takashima1, Ge Guo2, Remco Loos3
1Wellcome Trust-Medical Research Council Stem Cell Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK; PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan.
Cell
|September 13, 2014
概括
研究人员成功地通过表达NANOG和KLF2.2将人类干细胞重新编程到基本状态. 这种重新连接增强了自我更新和稳定性,模仿小鼠胚胎干细胞 (ESC) 进行潜在的治疗应用.
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.
- 分子遗传学 分子遗传学
背景情况:
- 人类多能干细胞 (hPSCs) 与小鼠ESC不同,因为它们具有不同的转录因子网络.
- 在hPSC中实现稳定,基态多能性对于再生医学至关重要.
研究的目的:
- 在人类细胞中设计一个功能性的基态多能电路.
- 为了研究基底状态多能诱导的分子机制.
主要方法:
- 暂时表达NANOG和KLF2以启动网络重新布线.
- 抑制ERK和蛋白激酶C通路以维持重置状态.
- 分析自我更新,差异化潜力,新陈代谢,DNA甲基化和转录组.
主要成果:
- 短期NANOG和KLF2表达成功将hPSC重置到基本状态.
- 抑制特定的信号通路维持了一个转基因独立的,重新连接状态.
- 重置细胞表现出增强的自我更新,稳定性和类似于ESCs的代谢配置文件.
- 观察到DNA甲基化和转录组重新调整的全球减少.
- 基本状态转录因子 (TFCP2L1,KLF4) 对于维持重置状态至关重要.
结论:
- 在人体细胞中安装和传播基本状态多能性的功能控制电路是可行的.
- 这种方法为研究和治疗提供了一条产生更强壮和类似ESC的多能细胞的途径.
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