在利基形成之前,WNT-SHH对抗性指定和扩展干细胞
Tamara Ouspenskaia1, Irina Matos1, Aaron F Mertz1
1Robin Neustein Laboratory of Mammalian Development and Cell Biology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10065, USA.
Cell
|January 16, 2016
概括
干细胞 (SCs) 通过不对称的细胞分裂独立地被指定和调节. 这一过程决定了子细胞是否成为干细胞或祖细胞,控制了它们的扩张和分化.
科学领域:
- 发育生物学
- 干细胞生物学
- 细胞信号传输
背景情况:
- 成人干细胞 (SC) 的维持和分化传统上被理解为由利基来源的信号来调节.
- 规范SC规范的精确机制及其监管途径的启动仍然是积极调查的领域.
研究的目的:
- 研究干细胞 (SC) 规范和调控的利基独立机制.
- 阐明WNT和SHH信号在头发芽发育过程中早期SC命运的作用.
主要方法:
- 免疫光显微镜
- 现场成像技术
- 基因操纵和血统追踪
- 细胞周期分析
- 在子宫内进行静脉病毒转导
主要成果:
- 在发育的毛囊中不对称的细胞分裂通过差异性WNT和SHH信号产生SCs.
- 具有较低WNT信号的超基底子成为SCs,对膜SHH做出反应,并对称扩大.
- 有高WNT信号的基位子保持缓慢循环,不对称的分裂并成为祖先,而不会对SHH做出反应.
- 这种机制确定并取代早期的SC,在限制它们的数量之前促进扩张.
结论:
- 干细胞命运和调节可以通过内在的,独立于的不对称细胞分裂来启动.
- 在不对称的分裂过程中差异性WNT和SHH信号决定子细胞的命运,建立干细胞或祖细胞.
- 这种内在机制为我们提供了关于干细胞群体最初是如何被指定和随后在发育过程中被调节的新理解.
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