Department of Laboratory Medicine and Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai,PR China.
PLoS One. 2013 Jul 18;8(7):e68990. doi: 10.1371/journal.pone.0068990. Print 2013.
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.
miRNAs 影响细胞命运决定的机制仍知之甚少。在此，我们报告 miR-200a 可抑制小鼠胚胎干细胞（ES 细胞）向内胚层和中胚层的分化。有趣的是，miR-200a 可直接靶向生长因子受体结合蛋白 2（Grb2），Grb2 是 Erk 信号通路中的关键衔接蛋白。此外，高水平的 miR-200a 可显著降低 Grb2 水平，并抑制胚状体形成中的中胚层和内胚层谱系的出现，同时抑制 Erk 的激活。最后，Grb2 的补充可显著挽救 miR-200a 诱导的层形成偏倚和 Erk 抑制。总之，我们的研究结果表明，miR-200a 通过直接调节 Grb2 表达和 Erk 信号通路，在 ES 细胞谱系决定中发挥关键作用。
