Role of BMP4 in hESC derived endothelial progenitors

描述（由申请人提供）：人胚胎干细胞（hESC）可潜在地用作血管发育、血管生成、血管发病机制、药物发现和组织工程的模型。然而，很少有人知道的机制控制hESC分化沿着途径向内皮细胞谱系。例如，骨形态发生蛋白（BMP）4，一种有效的中胚层诱导剂，已知在各种动物模型中的血管发育中起作用，但尚不清楚BMP 4在人类血管发生中起什么作用。在这里，我们已经开发了一个模型的hESC分化的基础上胚状体粘附在基质胶基质中EGM-2培养基。培养7天后，我们通过RT-PCR检测到内皮标志物（例如KDR、VE-Cad、PECAM 1、CD 34、eNOS、vWF、Tie-2）的表达显著增加。我们的初步结果表明，一个相对简单的hESC发育血管发生模型可以用来研究时间基因的表达，因此我们建议检查BMP 4在hESC分化和内皮发育中的作用。本研究中使用的细胞系的NIH hESC登记代码为：BG 01、BG 02和WA 09。

DESCRIPTION (provided by applicant): Human embryonic stem cells (hESC) can potentially be used as models of vascular development, angiogenesis, vascular pathogenesis, drug discovery and tissue engineering. Yet little is known about the mechanisms controlling hESC differentiation along the pathway toward the endothelial lineage. For example, bone morphogenic protein (BMP) 4, a potent mesoderm inducer, is known to play a role in vascular development in various animal models but it is unclear what role BMP4 plays in human vasculogenesis. Here we have developed a model of hESC differentiation based on embryoid bodies adhering to a Matrigel gel substrate in EGM-2 medium. After 7 days in culture we detected by RT-PCR significantly increased expression of endothelial markers (e.g. KDR, VE-Cad, PECAM1, CD34, eNOS, vWF, Tie-2). Our preliminary results indicate that a relatively simple hESC developmental vasculogenesis model may be used to study temporal gene expression therefore we propose to examine the role of BMP4 in the hESC differentiation and endothelial development. The NIH hESC registry codes for cell lines used in this research are:BG01,BG02 and WA09.