MicroRNA-127 Promotes Mesendoderm Differentiation of Mouse Embryonic Stem Cells by Targeting Left-Right Determination Factor 2
- Ma, H., Lin, Y., Zhao, Z.A., Lu, X., Yu, Y., Zhang, X., Wang, Q., Li, L.
- The Journal of biological chemistry 291: 12126-35 (Journal)
- Registered Authors
- Li, Lei, Wang, Qiang
- SMAD transcription factor, activin, development, embryonic stem cell, germ layer specification, left-right determination factor 2 (LEFTY2), microRNA (miRNA)
- MeSH Terms
- Blotting, Western
- Cell Differentiation/genetics*
- Cells, Cultured
- Embryo, Mammalian/cytology
- Embryo, Mammalian/embryology
- Embryo, Mammalian/metabolism
- Gene Expression Profiling
- Gene Expression Regulation, Developmental
- In Situ Hybridization
- Left-Right Determination Factors/genetics*
- Left-Right Determination Factors/metabolism
- Mouse Embryonic Stem Cells/metabolism*
- Nodal Protein/genetics
- Nodal Protein/metabolism
- Oligonucleotide Array Sequence Analysis
- Reverse Transcriptase Polymerase Chain Reaction
- Signal Transduction/genetics
- 27072135 Full text @ J. Biol. Chem.
Ma, H., Lin, Y., Zhao, Z.A., Lu, X., Yu, Y., Zhang, X., Wang, Q., Li, L. (2016) MicroRNA-127 Promotes Mesendoderm Differentiation of Mouse Embryonic Stem Cells by Targeting Left-Right Determination Factor 2. The Journal of biological chemistry. 291:12126-35.
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.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes