Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10891291 | Stem Cell Research | 2013 | 15 Pages |
Abstract
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 3â² 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.
Keywords
PBSLIFqPCRTuj1LSD1SSCddPCRDAPI3′ untranslated region3′UTR4,6-diamidino-2-phenylindole dihydrochlorideembryoid bodylysine specific demethylase 1reverse transcriptionsaline-sodium citrateES cellsEmbryonic stem cellsleukemia inhibitory factorPhosphate buffered salineDroplet digital PCRMicroRNAMiRNAquantitative real-time polymerase chain reaction
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Authors
Ke Jiang, Chunyan Ren, Venugopalan D. Nair,