MicroRNA-200a Regulates Grb2 and Suppresses Differentiation of Mouse Embryonic Stem Cells into Endoderm and Mesoderm |
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| Authors: | Yang Liu Qidong Liu Wenwen Jia Jie Chen Jianmin Wang Dan Ye Xudong Guo Wen Chen Guoping Li Guiying Wang Anmei Deng Jiuhong Kang |
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| Institution: | 1. Department of Laboratory Medicine and Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China.; 2. Clinical and Translational Research Center of Shanghai First Maternity and Infant Health Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, People’s Republic of China.; Centro Cardiologico Monzino, Italy, |
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| Abstract: | 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. |
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