Open AccessMicroRNA-200a Regulates Grb2 and Suppresses Differentiation of Mouse Embryonic Stem Cells into Endoderm and Mesoderm
Author(s) -
Yang Liu,
Qidong Liu,
Wenwen Jia,
Jie Chen,
Jianmin Wang,
Dan Ye,
Xudong Guo,
Wen Chen,
Guoping Li,
Guiying Wang,
Anmei Deng,
Jiuhong Kang
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0068990
Subject(s) - endoderm , microbiology and biotechnology , fgf and mesoderm formation , mesoderm , biology , mapk/erk pathway , grb2 , embryonic stem cell , cellular differentiation , embryoid body , stem cell , signal transduction , signal transducing adaptor protein , genetics , adult stem cell , gene
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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