常见的ERK诱导模式通过新兴网络和细胞类型特定的转录抑制分解为特定环境的信号
Marta Perera1, Joshua M Brickman1
1reNEW UCPH - The Novo Nordisk Foundation Center for Stem Cell Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen N, Denmark.
概括
纤维细胞生长因子 (FGF) 通过ERK发出信号,在早期发育中具有相反的作用. 在早期胚胎中,ERK促进了分化,但在后期阶段自我更新,背景决定了结果.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 分子信号传输的方法
背景情况:
- 纤维细胞生长因子 (FGF) 通过ERK (细胞外信号调节激酶) 发出信号,在胚胎发育和疾病中起着关键作用.
- 矛盾的是,ERK信号在早期的哺乳动物胚胎和天真的多能干细胞中促进了分化,但在初始化的多能干细胞中维持了自我更新.
研究的目的:
- 调查不同多能细胞状态下依赖上下文的ERK信号结果背后的机制.
- 了解相同的信号通路如何引起不同的细胞反应.
主要方法:
- 产生细胞和小鼠线,使ERK信号的组织和时间特定激活.
- 对转录位和染色质可访问性变化的分析,以响应ERK激活.
主要成果:
- 激活ERK通路会在很大程度上引起细胞类型之间保存的即时早期反应.
- 细胞类型的特异性源于不同的转录标的抑制和相关的染色质可访问性的变化.
- 染色体修饰伴随着ERK诱导在原始多能性中,但不是在后期阶段,表明取决于上下文的调节.
结论:
- 对ERK信号的细胞类型特定反应是通过塑造保存的即时早期反应来实现的.
- 结果的分歧是由特定细胞程序的抑制介导的,受细胞发育背景和染色质状态的影响.
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