Figure 7.

Schematic representation of the autocrine VEGF signaling in mESCs. Production of VEGF is activated via HIF1α and/or ER stress, presumably due to environmental stress in the in vitro culture. VEGF activates VEGFRs expressed on the surface of the mESCs, inducing the activation of MEK, GSK3β and possibly other pathways that promote differentiation and lineage commitment of mESCs. Blocking VEGFRs with sunitinib inhibits both the MEK and GSK3 pathways and the feed-forward loop between HIF1α/ER stress and VEGF/VEGFR, and thus prevents the spontaneous differentiation of mESCs.