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首页> 外文期刊>Acta Pharmacologica Sinica >Effect of leukemia inhibitory factor on embryonic stem cell differentiation: implications for supporting neuronal differentiation
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Effect of leukemia inhibitory factor on embryonic stem cell differentiation: implications for supporting neuronal differentiation

机译:白血病抑制因子对胚胎干细胞分化的影响:支持神经元分化的意义。

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Aim: Leukemia inhibitory factor (LIF), a pleiotropic cytokine, has been used extensively in the maintenance of mouse embryonic stem cell pluripotency. In this current work, we examined the effect of the LIF signaling pathway in embryonic stem (ES) cell differentiation to a neural fate. Methods: In the presence of LIF (1000 U/mL), the production of neuronal cells derived from embryoid bodies (EB) was tested under various culture conditions. Inhibition of the LIF pathway was examined with specific inhibitors. The effects of cell apoptosis and proliferation on neural differentiation were examined. ES cell differentiation into three-germ layers was compared. Results: Under various culture conditions, neuronal differentiation was increased in the presence of LIF. Blocking the LIF-activated STAT3 signaling pathway with specific inhibitors abolished the neuronal differentiation of ES cells, whereas inhibition of the LIF-activated MEK signaling pathway impaired the differentiation of ES cells toward a glial fate. LIF suppressed cell apoptosis and promoted cell proliferation during ES cell differentiation. LIF inhibited the differentiation of ES cells to both mesoderm and extraembryonic endo-derm fates, but enhanced the determination of neural progenitors. Conclusion: These results suggest that LIF plays a positive role during the differentiation of ES cells into neuronal cells.
机译:目的:多效性细胞因子白血病抑制因子(LIF)已广泛用于维持小鼠胚胎干细胞的多能性。在当前的工作中,我们检查了LIF信号通路在胚胎干(ES)细胞分化为神经命运中的作用。方法:在存在LIF(1000 U / mL)的情况下,在各种培养条件下测试源自胚状体(EB)的神经元细胞的产生。用特异性抑制剂检查了LIF途径的抑制作用。检查了细胞凋亡和增殖对神经分化的影响。比较了ES细胞分化为三层细菌的能力。结果:在各种培养条件下,存在LIF时神经元分化均增加。用特异性抑制剂阻断LIF激活的STAT3信号通路消除了ES细胞的神经元分化,而LIF激活的MEK信号通路的抑制作用则削弱了ES细胞向神经胶质命运的分化。 LIF抑制ES细胞分化过程中的细胞凋亡并促进细胞增殖。 LIF抑制ES细胞向中胚层和胚外内胚层命运的分化,但增强了神经祖细胞的测定。结论:这些结果表明,LIF在ES细胞分化为神经元细胞的过程中发挥了积极作用。

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