Stromal cell-derived Factor-1/CXCR4 signaling modifies the capillary-like organization of human embryonic stem cell-derived endothelium in vitro
Stromal cell-derived Factor-1/CXCR4 signaling modifies the capillary-like organization of human embryonic stem cell-derived endothelium in vitro
复制标题
基质细胞衍生的 Factor-1/CXCR4 信号传导在体外改变人胚胎干细胞衍生的内皮细胞的毛细血管样组织
DOI：
10.1634/stemcells.2006-0145
复制
发表时间：
2007-02-01
期刊：
影响因子：
5.2
通讯作者：
Wang, Zack Z.
中科院分区：
文献类型：
--
作者：
Chen, Tong;Bai, Hao;Wang, Zack Z.
在早期发育过程中调节人类血管形成的分子机制在很大程度上是未知的。在这里，我们使用人类ESCs （hESCs）作为体外模型来探索早期人类血管发生。我们证明基质细胞衍生因子-1 （SDF-1）和CXCR4在hesc衍生的胚胎内皮分化过程中同时表达。人esc来源的胚胎内皮细胞对SDF-1具有剂量依赖性的趋化性，这增强了Matrigel血管网络的形成。阻断CXCR4信号通路可消除SDF-1诱导的毛细血管样结构。CXCR4拮抗剂AMD3100抑制SDF-1/CXCR4信号通路，破坏了人胚状体的内皮发芽生长，表明SDF-1/CXCR4轴在调节初始血管形成中起关键作用，并可能在人胚胎血管发育过程中发挥形态因子的作用。
The molecular mechanisms that regulate human blood vessel formation during early development are largely unknown. Here we used human ESCs (hESCs) as an in vitro model to explore early human vasculogenesis. We demonstrated that stromal cell-derived factor-1 (SDF-1) and CXCR4 were expressed concurrently with hESC-derived embryonic endothelial differentiation. Human ESC-derived embryonic endothelial cells underwent dose-dependent chemotaxis to SDF-1, which enhanced vascular network formation in Matrigel. Blocking of CXCR4 signaling abolished capillary-like structures induced by SDF-1. Inhibition of the SDF-1/CXCR4 signaling pathway by AMD3100, a CXCR4 antagonist, disrupted the endothelial sprouting outgrowth from human embryoid bodies, suggesting that the SDF-1/CXCR4 axis plays a critical role in regulating initial vessel formation, and may function as a morphogen during human embryonic vascular development.