Leukemia inhibitory factor-induced Stat3 signaling suppresses fibroblast growth factor 1-induced Erk1/2 activation to inhibit the downstream differentiation in mouse embryonic stem cells.

In regular culture conditions with leukemia inhibitory factor (LIF), the majority of mouse embryonic stem cells (mESCs) are maintained in a self-renewal stage; very few mESCs have differentiated morphology. When LIF is withdrawn, mESCs tend to differentiate; this differentiation process can be enhanced by the introduction of exogenous fibroblast growth factor (FGF). Here, we show that even in the presence of exogenous FGF1, mESCs can maintain self-renewal and expression of pluripotency markers in the presence of LIF. To elucidate the mechanism in which LIF dominates over the FGF1, extracellular signal-regulated kinase 1/2 (Erk1/2) signaling of mESCs cultured in a medium containing FGF1 or LIF/FGF1 was examined. The results demonstrate that Erk1/2 was activated by FGF1 in the absence of LIF; however, the FGF1-induced Erk1/2 phosphorylation was suppressed when LIF was introduced. Moreover, FGF1-Erk1/2 downregulation was inhibited by a signal transducer and activator of the transcription 3 (Stat3) inhibitor ...