MicroRNA-200a Regulates Grb2 and Suppresses Differentiation of Mouse Embryonic Stem Cells into Endoderm and Mesoderm
MicroRNA-200a Regulates Grb2 and Suppresses Differentiation of Mouse Embryonic Stem Cells into Endoderm and Mesoderm
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MicroRNA-200a 调节 Grb2 并抑制小鼠胚胎干细胞分化为内胚层和中胚层
DOI：
10.1371/journal.pone.0068990
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发表时间：
2013-07-18
期刊：
影响因子：
3.7
通讯作者：
Kang, Jiuhong
中科院分区：
文献类型：
--
作者：
Liu, Yang;Liu, Qidong;Kang, Jiuhong
MicroRNAs(MiRNAs)影响细胞命运决定的机制仍然知之甚少。在此，我们报道了miR-200A可以抑制小鼠胚胎干细胞向内胚层和中胚层的分化。有趣的是，miR-200A直接靶向生长因子受体结合蛋白2(Grb2)，它是ERK信号通路中的一个关键适配器。此外，高水平的miR-200A显著降低Grb2的水平，抑制类胚体形成过程中中胚层和内胚层谱系的出现，并抑制ERK的激活。最后，补充Grb2显著挽救了miR-200A诱导的成层偏差和ERK抑制。总之，我们的结果表明miR-200A通过直接调节Grb2的表达和ERK信号在ES细胞谱系承诺中发挥关键作用。
The mechanisms by which microRNAs (miRNAs) affect cell fate decisions remain poorly understood. Herein, we report that miR-200a can suppress the differentiation of mouse embryonic stem (ES) cells into endoderm and mesoderm. Interestingly, miR-200a directly targets growth factor receptor-bound protein 2 (Grb2), which is a key adaptor in the Erk signaling pathway. Furthermore, high levels of miR-200a dramatically decrease Grb2 levels and suppress the appearance of mesoderm and endoderm lineages in embryoid body formation, as well as suppressing the activation of Erk. Finally, Grb2 supplementation significantly rescues the miR-200a-induced layer-formation bias and the Erk suppression. Collectively, our results demonstrate that miR-200a plays critical roles in ES cell lineage commitment by directly regulating Grb2 expression and Erk signaling.