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动脉化需要及时抑制细胞生长
2020-12-12 19:31

西班牙国家心血管研究中心(CNIC)Rui Benedito研究组取得一项新突破。他们发现动脉化需要及时抑制细胞生长。这一研究成果发表在2020年12月9日出版的《自然》杂志上。

他们结合可诱导的遗传镶嵌和转录组学来调节和定义这些信号通路在细胞增殖、动静脉分化和动员中的功能。他们显示,具有高水平的VEGF或Notch信号传导的内皮细胞固有地偏向于动员并形成动脉。但是,它们不是遗传预定的,还可以形成静脉。

从机理上讲,他们发现动脉前毛细血管中VEGF和Notch信号的水平升高抑制了MYC依赖性代谢和细胞周期活动,并促进了内皮细胞整合入动脉。镶嵌谱系追踪研究表明,缺少Notch-RBPJ转录激活因子复合物的内皮细胞很少形成动脉。然而,当MYC的功能被抑制时,这些细胞恢复了形成动脉的能力。

因此,动脉的发育不需要直接诱导Notch依赖性动脉分化程序,而是取决于及时抑制内皮细胞周期进程和新陈代谢,这是在动脉动员和完全分化之前的过程。

研究人员表示,据认为,动脉的形成是通过在一部分血管中诱导高度保守的动脉遗传程序而发生的,随后该血管会增加氧化的血流。动脉特化的初始步骤需要VEGF和Notch信号通路。

附:英文原文

Title: Arterialization requires the timely suppression of cell growth

Author: Wen Luo, Irene Garcia-Gonzalez, Macarena Fernndez-Chacn, Vernica Casquero-Garcia, Maria S. Sanchez-Muoz, Severin Mhleder, Lourdes Garcia-Ortega, Jorge Andrade, Michael Potente, Rui Benedito

Issue&Volume: 2020-12-09

Abstract: The formation of arteries is thought to occur by the induction of a highly conserved arterial genetic programme in a subset of vessels that will later experience an increase in oxygenated blood flow1,2. The initial steps of arterial specification require both the VEGF and Notch signalling pathways3,4,5. Here, we combine inducible genetic mosaics and transcriptomics to modulate and define the function of these signalling pathways in cell proliferation, arteriovenous differentiation and mobilization. We show that endothelial cells with high levels of VEGF or Notch signalling are intrinsically biased to mobilize and form arteries; however, they are not genetically pre-determined, and can also form veins. Mechanistically, we found that increased levels of VEGF and Notch signalling in pre-arterial capillaries suppresses MYC-dependent metabolic and cell-cycle activities, and promotes the incorporation of endothelial cells into arteries. Mosaic lineage-tracing studies showed that endothelial cells that lack the Notch–RBPJ transcriptional activator complex rarely form arteries; however, these cells regained the ability to form arteries when the function of MYC was suppressed. Thus, the development of arteries does not require the direct induction of a Notch-dependent arterial differentiation programme, but instead depends on the timely suppression of endothelial cell-cycle progression and metabolism, a process that precedes arterial mobilization and complete differentiation.

DOI: 10.1038/s41586-020-3018-x

Source: https://www.nature.com/articles/s41586-020-3018-x

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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