title: MicroRNA-127 Promotes Mesendoderm Differentiation of Mouse Embryonic Stem Cells by Targeting Left-Right Determination Factor 2.
abstract: Specification of the three germ layers is a fundamental process and is essential for the establishment of organ rudiments. Multiple genetic and epigenetic factors regulate this dynamic process; however, the function of specific microRNAs in germ layer differentiation remains unknown. In this study, we established that microRNA-127 (miR-127) is related to germ layer specification via microRNA array analysis of isolated three germ layers of E7.5 mouse embryos and was verified through differentiation of mouse embryonic stem cells. miR-127 is highly expressed in endoderm and primitive streak. Overexpression of miR-127 increases and inhibition of miR-127 decreases the expression of mesendoderm markers. We further show that miR-127 promotes mesendoderm differentiation through the nodal pathway, a determinative signaling pathway in early embryogenesis. Using luciferase reporter assay, left-right determination factor 2 (Lefty2), an antagonist of nodal, is identified to be a novel target of miR-127. Furthermore, the role of miR-127 in mesendoderm differentiation is attenuated by Lefty2 overexpression. Altogether, our results indicate that miR-127 accelerates mesendoderm differentiation of mouse embryonic stem cells through nodal signaling by targeting Lefty2.
authors.affiliation: From the State Key Laboratory of Stem Cell and Reproductive Biology and the Institute of Zoology, University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing and.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lin
authors.affiliation: From the State Key Laboratory of Stem Cell and Reproductive Biology and.
authors.forename: Zhen-Ao
authors.initials: ZA
authors.lastname: Zhao
authors.affiliation: From the State Key Laboratory of Stem Cell and Reproductive Biology and.
authors.forename: Xukun
authors.initials: X
authors.lastname: Lu
authors.affiliation: From the State Key Laboratory of Stem Cell and Reproductive Biology and.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: From the State Key Laboratory of Stem Cell and Reproductive Biology and.
authors.forename: Xiaoxin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, 100101 Beijing and qiangwang@ioz.ac.cn.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: From the State Key Laboratory of Stem Cell and Reproductive Biology and the Institute of Zoology, University of Chinese Academy of Sciences, Beijing 100049, China lil@ioz.ac.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004622:Embryo, Mammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D004707:Endoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D055458:Left-Right Determination Factors / Q000235:genetics* / Q000378:metabolism; D008648:Mesoderm / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D000066450:Mouse Embryonic Stem Cells / Q000378:metabolism*; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D015027:Zebrafish / Q000196:embryology / Q000235:genetics
chemical_list: D055458:Left-Right Determination Factors; C526162:Lefty2 protein, mouse; D035683:MicroRNAs; C533109:Mirn127 microRNA, mouse; D055457:Nodal Protein; C526008:Nodal protein, mouse
keywords: SMAD transcription factor; activin; development; embryonic stem cell; germ layer specification; left-right determination factor 2 (LEFTY2); microRNA (miRNA)