Molecular mechanisms of endothelial differentiation.

The differentiation of embryonic stem cells along the endothelial cell lineage requires a tightly coordinated sequence of events that are regulated in both space and time. Although significant gaps remain in this process, major strides have been made over the past 10 years in identifying the growth factors, signal transduction pathways, and transcription factors that function together as critical mediators of this process. Examples of some of the signal transduction pathways include the hedgehog (HH), WNT, BMP, and Notch pathways. A complex interplay between growth factors, and activation of a variety of signal transduction pathways leads to the induction of transcriptional programs that promote the differentiation of embryonic stem cells along the endothelial lineage and ultimately into arterial, venous, and lymphatic endothelial cells. The purpose of this review is to summarize the recent advances in our understanding of the molecular mechanisms underlying endothelial differentiation.