Here, we demonstrate that as human embryonic stem cells (ESCs) exit the pluripotent state, NANOG can Progestogen play a key position in identifying lineage final result. It has previously been reported that BMPs induce differentiation of human ESCs into extraembryonic lineages. Here, we find that FGF2, acting via the MEK-ERK pathway, switches BMP4-induced human ESC differentiation final result to mesendoderm, characterized by the uniform expression of T (brachyury) and various primitive streak markers. We also discover that MEK-ERK signaling prolongs selleck chemical Estrogen Receptor inhibitor NANOG expression throughout BMP-induced differentiation, that forced NANOG expression outcomes in FGF-independent BMP4 induction of mesendoderm, and that knockdown of NANOG drastically reduces T induction. Together, our benefits demonstrate that FGF2 signaling switches the outcome of BMP4-induced differentiation of human ESCs by preserving NANOG amounts as a result of the MEK-ERK pathway.