Role of BMP4 in hESC derived endothelial progenitors

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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.