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Molecular mechanism underlying the difference in proliferation between placenta-derived and umbilical cord-derived mesenchymal stem cells

机译:分子机制的差异placenta-derived之间的扩散和脐cord-derived间充质干细胞

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The placenta and umbilical cord are pre-eminent candidate sources of mesenchymal stem cells (MSCs). However, placenta-derived MSCs (P-MSCs) showed greater proliferation capacity than umbilical cord-derived MSCs (UC-MSCs) in our study. We investigated the drivers of this proliferation difference and elucidated the mechanisms of proliferation regulation. Proteomic profiling and Gene Ontology (GO) functional enrichment were conducted to identify candidate proteins that may influence proliferation. Using lentiviral or small interfering RNA infection, we established overexpression and knockdown models and observed changes in cell proliferation to examine whether a relationship exists between the candidate proteins and proliferation capacity. Real-time quantitative polymerase chain reaction, western blot analysis, and immunofluorescence assays were conducted to elucidate the mechanisms underlying proliferation. Six candidate proteins were selected based on the results of proteomic profiling and GO functional enrichment. Through further validation, yes-associated protein 1 (YAP1) and β-catenin were confirmed to affect MSCs proliferation rates. YAP1 and β-catenin showed increased nuclear colocalization during cell expansion. YAP1 overexpression significantly enhanced proliferation capacity and upregulated the expression of both β-catenin and the transcriptional targets of Wnt signaling, CCND1, and c-MYC, whereas silencing β-catenin attenuated this influence. We found that YAP1 directly interacts with β-catenin in the nucleus to form a transcriptional YAP/β-catenin/TCF4 complex. Our study revealed that YAP1 and (3-catenin caused the different proliferation capacities of P-MSCs and UC-MSCs. Mechanism analysis showed that YAP1 stabilized the nuclear β-catenin protein, and also triggered the Wnt/(3-catenin pathway, promoting proliferation.
机译:胎盘和脐带是杰出的候选人的间充质干细胞来源(msc)。显示增殖能力大于脐cord-derived msc (UC-MSCs)在我们的研究。扩散的区别,阐明扩散机制的监管。分析和基因本体论(去)功能浓缩进行了确定候选人可能影响扩散的蛋白质。慢病毒感染或小干扰RNA,我们建立了超表达和可拆卸的模型和观察到的细胞增殖的变化检查是否存在之间的关系候选蛋白和增殖能力。实时定量聚合酶链反应免疫印迹分析和免疫荧光进行了化验,阐明机制潜在的扩散。选择基于蛋白质组学的结果分析和功能性浓缩。进一步验证,yes-associated蛋白质1(YAP1)和β连环蛋白被证实影响msc增殖率。显示核colocalization在增加细胞扩张。增强的扩散能力和调节表达的β连环蛋白和CCND1转录Wnt信号的目标,和原癌基因,而沉默β连环蛋白减毒这种影响。与β连环蛋白在细胞核中形成转录YAP /β连环蛋白/ TCF4复杂。研究显示,YAP1 (3-catenin造成P-MSCs的不同的增殖能力和UC-MSCs。稳定核β连环蛋白的蛋白质,也引发了Wnt / (3-catenin通路,促进扩散。

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