内源性FGF驱动ERK依赖的细胞命运模式在2D人类胃体中
Kyoung Jo1, Zong-Yuan Liu1, Gauri Patel2
1Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
概括
纤维细胞生长因子 (FGF) 信号驱动人体通过ERK激活胃流动,其中FGF4和FGF17诱导原始链状 (PS) 细胞. FGF8可能会限制这个过程,揭示了FGF在早期发育中的新角色.
科学领域:
- 发展生物学 发展生物学
- 细胞信号传递 细胞信号传递
- 人类胚胎发生
背景情况:
- 纤维细胞生长因子 (FGF) 信号传递在哺乳动物胃流动中至关重要,但人们对其了解甚少.
- 研究FGF在人类胃流中的作用对于了解早期发育至关重要.
研究的目的:
- 通过2D胃类型模型阐明FGF信号在人类胃发育中的功能.
- 确定特定的FGF配体及其在原始串状 (PS) 样细胞形成和分化中的作用.
主要方法:
- 利用一个2D胃形模型来模拟人类的胃流动.
- 分析了依赖FGF的ERK活动模式.
- 进行了单细胞转录组分析,以确定FGF连接体表达.
- 研究了FGF淘汰和受体抑制对PS类差异化的影响.
主要成果:
- 在PS样细胞出现之前和期间观察到FGF依赖的ERK活动.
- FGF4和FGF17在PS类细胞中得到特定的表达,并且对于分化是必需的.
- FGF8的表达被取代了,它的敲击扩展了PS类细胞,这表明它有抑制作用.
- 通过基底侧FGF受体1 (FGFR1) 作用,诱导PS类细胞.
结论:
- 通过FGFR1传递FGF4和FGF17信号对于诱导人体PS样细胞和其衍生物在胃类体中至关重要.
- 依赖于FGF的ERK信号在人类早期发育中起着新的,必不可少的作用.
- FGF8可能充当PS类分化的负调节者,与它在小鼠胚胎中的作用形成鲜明对比.
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