Characterization of the vasculogenic block in the absence of vascular endothelial growth factor-A
Characterization of the vasculogenic block in the absence of vascular endothelial growth factor-A
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DOI：
10.1182/blood.v95.6.1979
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发表时间：
2000-03-15
期刊：
影响因子：
20.3
通讯作者：
Rapoport, R
中科院分区：
文献类型：
--
作者：
Bautch, VL;Redick, SD;Rapoport, R
血管内皮生长因子（VEGF）信号传导是血管内皮细胞分化和增殖所必需的。分析一个或两个VEGF-A等位基因缺失的分化胚胎干细胞显示，在血管发生过程中，内皮细胞的分化和扩增都被阻断。在半合子突变型VEGF培养物中，血岛形成减少了一半，在纯合子突变型VEGF培养物中，血岛形成减少了10倍。纯合子突变培养物可以通过添加外源性VEGF部分地挽救，纯合子突变培养物中内皮粘附受体ICAM-2和PECAM的RNA水平降低，但ICAM-2 RNA水平大幅降低，而PECAM RNA水平保持在半合子水平。定量数据与抗体染色模式相关，因为未组织成血管的细胞表达PECAM，但不表达ICAM-2。这些PECAM+细胞团块随着血管密度降低而在突变培养物中积累，表明它们是被阻止成熟的内皮细胞前体。成团的PECAM+细胞亚群表达阶段特异性胚胎抗原-1（SSEA-1），且均为ICAM-2（-）和CD 34（-），而并入血管的血管内皮细胞为PECAM（+）、ICAM-2（+）、CD 34（+）和SSEA-1（-）。flk-1表达分析表明，血管前体细胞的一个子集共表达PECAM和flk-1。这些数据表明，VEGF信号传导以剂量依赖性方式影响内皮细胞的特异性分化步骤和随后的扩增。(C)2000年，美国血液学会。
Vascular endothelial growth factor (VEGF) signaling is required for both differentiation and proliferation of vascular endothelium. Analysis of differentiated embryonic stem cells with one or both VEGF-A alleles deleted showed that both the differentiation and the expansion of endothelial cells are blocked during vasculogenesis. Blood island formation was reduced by half in hemizygous mutant VEGF cultures and by 10-fold in homozygous mutant VEGF cultures. Homozygous mutant cultures could be partially rescued by the addition of exogenous VEGF, RNA levels for the endothelial adhesion receptors ICAM-2 and PECAM were reduced in homozygous mutant cultures, but ICAM-2 RNA levels decreased substantially, whereas PECAM RNA levels remained at hemizygous levels. The quantitative data correlated with the antibody staining patterns because cells that were not organized into vessels expressed PECAM but not ICAM-2. These PECAM+ cell clumps accumulated in mutant cultures as vessel density decreased, suggesting that they were endothelial cell precursors blocked from maturation. A subset of PECAM+ cells in clumps expressed stage-specific embryonic antigen-1 (SSEA-1), and all were ICAM-2(-) and CD34(-), whereas vascular endothelial cells incorporated into vessels were PECAM(+), ICAM-2(+), CD34(+), and SSEA-1(-). Analysis of flk-1 expression indicated that a subset of vascular precursor cells coexpressed PECAM and flk-1. These data suggest that VEGF signaling acts in a dose-dependent manner to affect both a specific differentiation step and the subsequent expansion of endothelial cells. (C) 2000 by The American Society of Hematology.