title: MicroRNA-200a regulates Grb2 and suppresses differentiation of mouse embryonic stem cells into endoderm and mesoderm.
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.
authors.affiliation: Department of Laboratory Medicine and Department of Hematology, Changhai Hospital, Second Military Medical University, Shanghai,PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Qidong
authors.initials: Q
authors.lastname: Liu
authors.forename: Wenwen
authors.initials: W
authors.lastname: Jia
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Ye
authors.forename: Xudong
authors.initials: X
authors.lastname: Guo
authors.forename: Wen
authors.initials: W
authors.lastname: Chen
authors.forename: Guoping
authors.initials: G
authors.lastname: Li
authors.forename: Guiying
authors.initials: G
authors.lastname: Wang
authors.forename: Anmei
authors.initials: A
authors.lastname: Deng
authors.forename: Jiuhong
authors.initials: J
authors.lastname: Kang
mesh_terms: D000469:Alkaline Phosphatase; D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D053595:Embryonic Stem Cells / Q000166:cytology*; D004707:Endoderm / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D051380:GRB2 Adaptor Protein / Q000378:metabolism*; D008156:Luciferases; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009841:Oligonucleotides / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D051380:GRB2 Adaptor Protein; D035683:MicroRNAs; C543719:Mirn200 microRNA, mouse; D009841:Oligonucleotides; D008156:Luciferases; D000469:Alkaline Phosphatase