Jiang Ke, Ren Chunyan, Nair Venugopalan D
Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Stem Cell Res. 2013 Nov;11(3):1299-313. doi: 10.1016/j.scr.2013.09.001. Epub 2013 Sep 13.
MicroRNA-137 (miR-137) has been shown to play an important role in the differentiation of neural stem cells. Embryonic stem (ES) cells have the potential to differentiate into different cell types including neurons; however, the contribution of miR-137 in the maintenance and differentiation of ES cells remains unknown. Here, we show that miR-137 is mainly expressed in ES cells at the mitotic phase of the cell cycle and highly upregulated during differentiation. We identify that ES cell transcription factors, Klf4 and Tbx3, are downstream targets of miR-137, and we show that endogenous miR-137 represses the 3' untranslated regions of Klf4 and Tbx3. Transfection of ES cells with mature miR-137 RNA duplexes led to a significant reduction in cell proliferation and the expression of Klf4, Tbx3, and other self-renewal genes. Furthermore, we demonstrate that increased miR-137 expression accelerates differentiation of ES cells in vitro. Loss of miR-137 during ES cell differentiation significantly impeded neuronal gene expression and morphogenesis. Taken together, our results suggest that miR-137 regulates ES cell proliferation and differentiation by repressing the expression of downstream targets, including Klf4 and Tbx3.
微小RNA - 137（miR - 137）已被证明在神经干细胞的分化中起重要作用。胚胎干细胞（ES细胞）有分化为包括神经元在内的不同细胞类型的潜力；然而，miR - 137在ES细胞维持和分化中的作用仍不清楚。在此，我们表明miR - 137主要在细胞周期的有丝分裂期的ES细胞中表达，并在分化过程中高度上调。我们确定ES细胞转录因子Klf4和Tbx3是miR - 137的下游靶点，并表明内源性miR - 137抑制Klf4和Tbx3的3'非翻译区。用成熟的miR - 137 RNA双链体转染ES细胞导致细胞增殖以及Klf4、Tbx3和其他自我更新基因的表达显著降低。此外，我们证明增加的miR - 137表达加速了ES细胞在体外的分化。ES细胞分化过程中miR - 137的缺失显著阻碍了神经元基因的表达和形态发生。综上所述，我们的结果表明miR - 137通过抑制包括Klf4和Tbx3在内的下游靶点的表达来调节ES细胞的增殖和分化。
