miR-142-3p Contributes to Early Cardiac Fate Decision of Embryonic Stem Cells.
miR-142-3p Contributes to Early Cardiac Fate Decision of Embryonic Stem Cells.
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miR-142-3p 有助于胚胎干细胞的早期心脏命运决定
DOI：
10.1155/2017/1769298
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发表时间：
2017
影响因子：
4.3
通讯作者：
Yang HT
中科院分区：
文献类型：
--
作者：
Chen ZY;Chen F;Cao N;Zhou ZW;Yang HT
microRNAs（miRNAs）在细胞命运决定中起着重要作用。然而，参与调节心脏谱系特化的miRNAs及其靶点在很大程度上未被探索。在此，我们报告了miR-142- 3 p在调节小鼠胚胎干细胞（mESC）向心肌细胞分化中的新功能。通过miRNA芯片筛选，我们鉴定了mESC向中胚层和心脏祖细胞分化过程中大量的miRNA发生了显著变化，miR-142- 3 p是其中一个显著下调的miRNA。miR-142- 3 p的异位表达和抑制并没有改变未分化胚胎干细胞的特征，而miR-142- 3 p的异位表达则损害心肌细胞的形成。此外，miR-142- 3 p的异位表达抑制心脏中胚层标记基因Mesp 1和下游心脏转录因子Nkx2.5、Tbx 5和Mef 2c的表达，但不抑制三个胚层特异性基因的表达。我们进一步证明了miR-142- 3 p靶向Mef 2c的3′-非翻译区。这些结果揭示了miR-142- 3 p作为早期心肌细胞分化的重要调节因子。我们的研究结果为进一步理解miRNAs作为心肌细胞分化的关键调节因子的作用和机制提供了新的知识。
MicroRNAs (miRNAs) play important roles in cell fate decisions. However, the miRNAs and their targets involved in the regulation of cardiac lineage specification are largely unexplored. Here, we report novel functions of miR-142-3p in the regulation of cardiomyocyte differentiation from mouse embryonic stem cells (mESCs). With a miRNA array screen, we identified a number of miRNAs significantly changed during mESC differentiation into the mesodermal and cardiac progenitor cells, and miR-142-3p was one among the markedly downregulated miRNAs. Ectopic expression and inhibition of miR-142-3p did not alter the characteristics of undifferentiated ESCs, whereas ectopic expression of miR-142-3p impaired cardiomyocyte formation. In addition, ectopic expression of miR-142-3p inhibited the expression of a cardiac mesodermal marker gene Mesp1 and downstream cardiac transcription factors Nkx2.5, Tbx5, and Mef2c but not the expression of three germ layer-specific genes. We further demonstrated that miR-142-3p targeted the 3′-untranslated region of Mef2c. These results reveal miR-142-3p as an important regulator of early cardiomyocyte differentiation. Our findings provide new knowledge for further understanding of roles and mechanisms of miRNAs as critical regulators of cardiomyocyte differentiation.