Role of BMP4 in hESC derived endothelial progenitors

描述(申请人提供)：人类胚胎干细胞(HESC)可能被用作血管发育、血管生成、血管发病机制、药物发现和组织工程的模型。然而，目前对控制hESC向内皮细胞分化的机制知之甚少。例如，骨形态发生蛋白(BMP)4是一种有效的中胚层诱导剂，已知在各种动物模型的血管发育中发挥作用，但尚不清楚BMP4在人类血管形成中扮演什么角色。在此，我们建立了一种基于类胚体在EGM-2培养液中附着于Matrigel凝胶底物上的hESC分化模型。培养7d后，RT-PCR检测内皮细胞标志物(如KDR、VE-Cad、PECAM1、CD34、eNOS、vWF、Tie-2)的表达显著增加。我们的初步结果表明，可以使用一个相对简单的hESC发育血管生成模型来研究时间基因的表达，因此我们建议研究BMP4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注册代码为：BG01、BG02和WA09。

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.