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动脉化需要及时抑制细胞生长
Wen Luo1, Irene Garcia-Gonzalez1, Macarena Fernández-Chacón1
1Molecular Genetics of Angiogenesis Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Nature
|December 10, 2020
概括
血管发育依赖于像VEGF和Notch这样的信号通路. 抑制细胞循环和新陈代谢, 而不是直接诱导动脉程序, 是形成动脉的关键.
科学领域:
- 发育生物学
- 血管生物学
- 细胞信号传输
背景情况:
- 动脉的形成与保存的遗传程序和增加的血液流动有关.
- 血管内皮生长因子 (VEGF) 和Notch信号通路对于最初的动脉特异性至关重要.
- 了解这些途径在细胞增殖和分化中的精确作用至关重要.
研究的目的:
- 研究VEGF和Notch信号在细胞增殖,动脉静脉分化和动员中的作用.
- 确定这些途径影响动脉和静脉形成的机制.
- 澄清信号通路,细胞循环,新陈代谢和动脉发育之间的关系.
主要方法:
- 使用可诱导的基因马赛克调节VEGF和Notch信号.
- 使用转录学来分析基因表达的变化.
- 进行了马赛克谱系追踪研究以追踪内皮细胞命运.
主要成果:
- 高VEGF或Notch信号使内皮细胞倾向于动员和形成动脉,但不会预先确定它们的命运.
- 增加的VEGF和Notch信号抑制了MYC依赖的细胞循环和毛细血管中的代谢活动,促进了动脉结合.
- 损失诺奇-RBPJ功能损害了动脉形成,可以通过抑制MYC来挽救.
结论:
- 动脉发育不是通过直接诱导依赖口的动脉程序来驱动的.
- 动脉特异性取决于内皮细胞循环进展和新陈代谢的及时抑制.
- 这种抑制在动脉动员和分化之前,突显了血管发育中的新机制.
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