细胞内pH控制胚胎糖解下游的WNT
Masayuki Oginuma1,2,3, Yukiko Harima1,2, Oscar A Tarazona1,2
1Department of Genetics, Harvard Medical School, Boston, MA, USA.
Nature
|June 26, 2020
概括
胚胎尾芽细胞使用有氧糖解,类似于癌细胞,以调节WNT信号并促进体长的中皮命运. 这种代谢过程会影响细胞在发育过程中的命运.
科学领域:
- 发育生物学
- 细胞代谢
- 癌症生物学
背景情况:
- 脊椎动物的胚胎体形成依赖于从尾部增加的组织.
- 尾茎细胞表现出高有氧糖解 (华堡效应),类似于癌细胞.
- 纤维细胞生长因子调节的糖解会影响尾芽中的WNT信号.
研究的目的:
- 研究葡萄糖溶解在尾芽中调节WNT信号的作用.
- 了解新陈代谢状态如何影响胚胎发育中的细胞命运决定.
- 探索发育代谢程序与癌细胞代谢之间的联系.
主要方法:
- 用胚胎进行体内研究.
- 在实验室中从诱导的多能干细胞中分化出人类尾部状细胞.
- 分析了pH梯度,通过单碳酸盐辅助剂的乳酸挤出和β-catenin乙化.
主要成果:
- 在尾芽细胞中观察到反向的pH梯度 (细胞外pH低于细胞内pH),类似于癌细胞.
- 证明糖解促进乳酸和质子挤出,增加细胞内pH值.
- 显示细胞内pH值升高促进非酶性β-catenin乙化,促进间皮性命运.
结论:
- 糖解通过调节细胞内pH和β-catenin乙化来调节尾芽细胞中的WNT信号.
- 这种新陈代谢途径对于指明近轴半皮和使轴延长成为可能至关重要.
- 这些发现表明癌细胞可能会重新激活发育代谢程序.
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