Vascular endothelial cells differentiated from pluripotent stem cells have potential in a variety of therapeutic areas such as tissue engineered vascular grafts and revascularization of ischemic tissues. However, there remain limitations in the control of stem cell differentiation into the desired functional phenotypes with current methods. During vascular development, it has been demonstrated that the early arterial-venous cell fate is genetically programmed, with the expression of transmembrane proteins ephrinB2 and EphB4 as the first distinction, prior to hemodynamic cues .
Here, we hypothesize that arterial venous differentiation is influenced, not only from the Notch activation pathway, but also from the bidirectional signaling of these transmembrane ligand-receptor proteins. Our results show ephrinB2/EphB4 immobilized signaling in combination with soluble factors can influence arterial venous differentiation in mouse embryonic stem cells (mESCs).