Tcf3控制干细胞特征,抑制皮肤中的细胞命运决定
Hoang Nguyen1, Michael Rendl, Elaine Fuchs
1Howard Hughes Medical Institute, Department of Mammalian Cell Biology and Development, The Rockefeller University, 1230 York Avenue, Box 300, New York, NY 10021, USA.
Cell
|October 5, 2006
概括
作为β-catenin的DNA结合伙伴,TCf3保持了皮肤干细胞 (SCs) 在没有Wnt信号的不分化状态. 在Wnt激活时,TCf3将SCs引导到毛细胞命运.
科学领域:
- 发育生物学 发展生物学
- 干细胞生物学 干细胞生物学
- 皮肤病学 皮肤病学
背景情况:
- 干细胞 (SCs) 通常依赖Wnt信号进行分化.
- 在没有Wnt信号的SC中,Tcf3作为β-catenin的DNA结合伙伴的作用尚不清楚.
- 皮肤原生体表达Tcf3并响应Wnt信号来决定毛细胞命运.
研究的目的:
- 为了研究皮肤干细胞中Tcf3的功能,在没有Wnt信号的情况下.
- 确定TCf3能否维持干细胞种群并影响分化途径.
- 阐明Tcf3在皮肤原生细胞的转录调节中的作用.
主要方法:
- 在小鼠中使用一种可诱导系统来控制皮肤祖先的Tcf3表达.
- 分析了在已承诺的表皮细胞中Tcf3重新激活后的基因表达变化.
- 研究了TCf3诱导对表皮,脂质腺和毛囊分化途径的影响.
主要成果:
- 在已承诺的表皮细胞中,TCf3的重新激活诱导了与未分化,Wnt抑制状态相关的基因.
- Tcf3促进了胚胎和产后皮肤干细胞共同的转录程序.
- Tcf3抑制了参与表皮,脂质腺和毛囊分化的基因,在诱导时抑制了这些途径.
结论:
- 在皮肤SC中,Tcf3的功能在没有Wnt信号的情况下保持不分化的状态.
- 与Tcf3相结合,Wnt信号将皮肤SCs引导到头发系的承诺.
- Tcf3在调节干细胞自我更新和皮肤分化之间的平衡方面发挥着至关重要的作用.
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