| الوصف: |
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 When LIF is withdrawn, mESCs tend to differentiate ; this differentiation process can be enhanced by the introduction of exogenous FGF.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 FGF1, extracellular signal-regulated kinase 1/2 (Erk1/2) signaling of mESCs cultured in 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 down-regulation was inhibited by signal transducer and activator of transcription 3 (Stat3) inhibitor WP1066, suggesting that LIF-induced Stat3 activation plays an important role in FGF1-Erk1/2 inhibition in mESCs. We further demonstrate that the binding affinity of phospho-Erk1/2 and Sprouty2 was increased via Stat3 activation. Binding of phospho-Erk1/2 and Sprouty2 blocks the activation of Erk1/2 signaling, and thus inhibits the downstream differentiation process in mESCs. Our findings demonstrate, for the first time, that LIF-induced Stat3 phosphorylation plays an important role in promoting the binding of phospho-Erk1/2 and Sprouty2, and thus inhibiting FGF1-induced differentiation. The feasibility of reprogramming human cells to induced neurons (iNs) was also explored in this study. Due to their high efficiency of generating functional neurons, the iNs show great potential in cell therapeutic medicine development. Most of nowadays studies use fibroblasts as the cell source for reprogramming. It would be beneficial to broaden the cell source for iNs. Taking the advantage of broadly banked blood cells, it is valuable to develop a blood cell ... |
