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首页> 外文期刊>Journal of Cellular Physiology >Disabled-2 is required for mesoderm differentiation of murine embryonic stem cells.
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Disabled-2 is required for mesoderm differentiation of murine embryonic stem cells.

机译：为中胚层Disabled-2是必需的小鼠胚胎干细胞的分化。

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A variety of signaling networks are implicated in the control of mesoderm differentiation. Previous studies demonstrated that Disabled-2 (DAB2) is a multifunctional protein involved in growth factor signaling and embryonic development. In this study, we investigated DAB2 expression and function during in vitro mesoderm differentiation of murine embryonic stem cells (ESCs). We found that DAB2 was up-regulated when ESCs were co-cultured with OP9 stromal cells for mesoderm differentiation. DAB2 was also up-regulated when ESCs were induced for embryoid body formation. Expression of DAB2 short hairpin small interfering RNA (shDAB2) did not alter the puripotency of ESCs. However, shDAB2 disrupted ESCs cell-cell adhesion and affected embryoid body and colony formation that subsequently impeded mesoderm differentiation of ESCs. Immunofluorescent staining revealed that disorganization of beta-catenin and plakoglobin cellular distribution may account for the aberrant cell-cell adhesion in DAB2-deficient cells. Accordingly, DAB2 was identified as a plakoglobin-binding partner with the interaction mediated by the phosphotyrosine binding domain of DAB2 and the Asn-Pro-Asp-Tyr (NPDY) motif of plakoglobin. Molecular analysis and transcriptome profiling also revealed that DAB2 was involved in the regulation of insulin-like growth factor 2-mediated signaling and in the expression of p53, asparagine synthetase and glutathione peroxidase 2. Expression screening of 52 ESCs-related miRNAs further unveiled the interplay between DAB2 and the signaling networks associated with cell death, differentiation and development. This study thereby defines a role of DAB2 in fate determination of ESCs and suggests the presence of a DAB2-associated regulatory circuit in the control of mesoderm differentiation.
机译：各种各样的信号网络涉及中胚层分化的控制。研究表明,Disabled-2 (DAB2)是一个多功能蛋白参与生长因子信号和胚胎发育。研究中,我们调查了DAB2表达式函数在试管中胚层分化小鼠胚胎干细胞(ESCs)。当ESCs表达,DAB2上调OP9基质细胞培养中胚层分化。ESCs身体被诱导胚状体的形成。表达DAB2短发夹小干扰RNA (shDAB2)并没有改变puripotency ESCs的。ESCs信息粘附和胚状体的影响随后的身体和集落形成阻碍的ESCs的中胚层分化。Immunofluorescent染色显示,混乱的β-连环蛋白和plakoglobin细胞分布可能占异常信息在DAB2-deficient附着力细胞。plakoglobin-binding伙伴的互动由phosphotyrosine绑定域DAB2和Asn-Pro-Asp-Tyr (NPDY)的主题plakoglobin。分析还显示,DAB2参与胰岛素样生长因子的调节2-mediated信号的表达式p53、天冬酰胺合成酶、谷胱甘肽过氧化物酶2。ESCs-related microrna进一步揭开了DAB2之间的相互作用和信号网络与细胞死亡有关,分化发展。ESCs DAB2在命运的决心和建议DAB2-associated监管的存在在中胚层的控制电路分化。

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