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Right here, we display that as human embryonic stem cells (ESCs) exit the pluripotent state, NANOG can FAAH play a critical role in figuring out lineage final result. It has previously been reported that BMPs induce differentiation of human ESCs into extraembryonic lineages. Right here, we find that FGF2, acting by means of the MEK-ERK pathway, switches BMP4-induced human ESC differentiation final result to mesendoderm, characterized through the uniform expression of T (brachyury) together with other primitive streak markers. We also discover that MEK-ERK signaling prolongs selleck inhibitor NANOG expression all through BMP-induced differentiation, that forced NANOG expression success in FGF-independent BMP4 induction of mesendoderm, and that knockdown of NANOG significantly decreases T induction. Together, our outcomes demonstrate that FGF2 signaling switches the end result of BMP4-induced differentiation of human ESCs by preserving NANOG amounts via the MEK-ERK pathway.