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MiR‐184 directly targets Wnt3 in cardiac mesoderm differentiation of embryonic stem cells
STEM CELLS ( IF 4.0 ) Pub Date : 2020-09-30 , DOI: 10.1002/stem.3282 Xiaoqin Liu 1 , Yiwei Yang 1 , Xing Wang 1 , Xudong Guo 1 , Chenqi Lu 2 , Jiuhong Kang 1 , Guiying Wang 1
STEM CELLS ( IF 4.0 ) Pub Date : 2020-09-30 , DOI: 10.1002/stem.3282 Xiaoqin Liu 1 , Yiwei Yang 1 , Xing Wang 1 , Xudong Guo 1 , Chenqi Lu 2 , Jiuhong Kang 1 , Guiying Wang 1
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Embryonic stem (ES) cells have the property of self‐renewal and multi‐directional differentiation, and provide an ideal model for studying early embryo development in vitro. Wnt3, as Wnt family member 3, plays a vital role during ES cell differentiation. However, the exact regulatory mechanism of Wnt3 remains to be elucidated. MicroRNAs can directly regulate gene expression at the post‐transcriptional level and play critical function in cell fate determination. Here, we found the expression level of miR‐184 decreased when ES cells differentiated into cardiac mesoderm then increased during the process as differentiated into cardiomyocytes, which negatively correlated with the expression of Wnt3. Overexpression of miR‐184 during the process of ES cell differentiation into cardiac mesoderm repressed cardiac mesoderm differentiation and cardiomyocyte formation. Bioinformatics prediction and mechanism studies showed that miR‐184 directly bound to the 3′UTR region of Wnt3 and inhibited the expression level of Wnt3. Consistently, knockdown of Wnt3 mimicked the effects of miR‐184‐overexpression on ES cell differentiation into cardiac mesoderm, whereas overexpression of Wnt3 rescued the inhibition effects of miR‐184 overexpression on ES cell differentiation. These findings demonstrated that miR‐184 is a direct regulator of Wnt3 during the differentiation process of ES cells, further enriched the epigenetic regulatory network of ES cell differentiation into cardiac mesoderm and cardiomyocytes.
中文翻译：
MiR-184在胚胎干细胞心脏中胚层分化中直接靶向Wnt3
胚胎干细胞（ES）具有自我更新和多向分化的特性，为体外研究早期胚胎发育提供了理想的模型。 Wnt3作为Wnt家族成员3，在ES细胞分化过程中发挥着至关重要的作用。然而，Wnt3的确切调控机制仍有待阐明。 MicroRNA可以在转录后水平直接调节基因表达，并在细胞命运决定中发挥关键作用。在这里，我们发现当ES细胞分化为心脏中胚层时，miR-184的表达水平下降，而在分化为心肌细胞的过程中，miR-184的表达水平增加，这与Wnt3的表达呈负相关。 ES细胞分化为心脏中胚层过程中miR-184的过度表达抑制了心脏中胚层分化和心肌细胞形成。生物信息学预测和机制研究表明，miR-184直接结合Wnt3的3'UTR区域并抑制Wnt3的表达水平。一致地， Wnt3的敲低模拟了miR-184过表达对ES细胞分化为心脏中胚层的影响，而Wnt3的过表达则挽救了miR-184过表达对ES细胞分化的抑制作用。这些研究结果表明，miR-184在ES细胞分化过程中是Wnt3的直接调节因子，进一步丰富了ES细胞分化为心脏中胚层和心肌细胞的表观遗传调控网络。
更新日期：2020-12-02
中文翻译：
MiR-184在胚胎干细胞心脏中胚层分化中直接靶向Wnt3
胚胎干细胞（ES）具有自我更新和多向分化的特性，为体外研究早期胚胎发育提供了理想的模型。 Wnt3作为Wnt家族成员3，在ES细胞分化过程中发挥着至关重要的作用。然而，Wnt3的确切调控机制仍有待阐明。 MicroRNA可以在转录后水平直接调节基因表达，并在细胞命运决定中发挥关键作用。在这里，我们发现当ES细胞分化为心脏中胚层时，miR-184的表达水平下降，而在分化为心肌细胞的过程中，miR-184的表达水平增加，这与Wnt3的表达呈负相关。 ES细胞分化为心脏中胚层过程中miR-184的过度表达抑制了心脏中胚层分化和心肌细胞形成。生物信息学预测和机制研究表明，miR-184直接结合Wnt3的3'UTR区域并抑制Wnt3的表达水平。一致地， Wnt3的敲低模拟了miR-184过表达对ES细胞分化为心脏中胚层的影响，而Wnt3的过表达则挽救了miR-184过表达对ES细胞分化的抑制作用。这些研究结果表明，miR-184在ES细胞分化过程中是Wnt3的直接调节因子，进一步丰富了ES细胞分化为心脏中胚层和心肌细胞的表观遗传调控网络。
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