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首页> 外文期刊>BMC Biotechnology >Mild electrical stimulation with heat shock guides differentiation of embryonic stem cells into Pdx1-expressing cells within the definitive endoderm
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Mild electrical stimulation with heat shock guides differentiation of embryonic stem cells into Pdx1-expressing cells within the definitive endoderm

机译：轻度的热刺激电刺激可将胚胎干细胞分化为定形内胚层中表达Pdx1的细胞

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BackgroundBecause of the increasing number of diabetic patients, it is important to generate pancreatic and duodenal homeobox gene 1 (Pdx1)-expressing cells, which are capable of differentiating into pancreatic endocrine β cells. Mild electrical stimulation was reported to modulate the differentiation of ES cells into ectoderm-derived neuronal cells or mesoderm-derived cardiac cells. ResultsIn this study, we report that mild electrical stimulation with heat shock (MET) potentiates the differentiation of ES cells into definitive endoderm-derived Pdx1-expressing cells. MET has no effect when applied to early definitive endoderm on differentiation day 5. A 1.87-fold increase in the proportion of Pdx1-expressing cells was observed when stimulation was applied to the late definitive endoderm one day prior to the immergence of Pdx1 /GFP-expressing cells on differentiation day 7. Pdx1 mRNA was also up-regulated by MET. The potentiating effect of MET synergized with activin and basic fibroblast growth factor into Pdx1-expressing cells. Moreover, MET stimulation on late definitive endoderm up-regulated heat shock protein 72 and activated various kinases including Akt, extracellular signal-regulated kinase, p38, and c-jun NH2-terminal kinase in ES cells. ConclusionsOur findings indicate that MET induces the differentiation of Pdx1-expressing cells within the definitive endoderm in a time-dependent manner, and suggest useful application for regenerative medicine.
机译：背景技术由于糖尿病患者的数量不断增加，因此重要的是要产生能够分化为胰腺内分泌β细胞的表达胰腺和十二指肠同源盒基因1（Pdx1）的细胞。据报道，轻度电刺激可调节ES细胞分化为外胚层来源的神经元细胞或中胚层来源的心脏细胞。结果在这项研究中，我们报道了轻度的热激电刺激（MET）刺激了ES细胞向内胚层衍生的Pdx1表达细胞的分化。当在分化第5天将其应用于早期定形内胚层时，MET无效。当在浸入Pdx1 / GFP-前一天对晚期定形内胚层施加刺激时，观察到Pdx1表达细胞比例增加1.87倍。在分化第7天表达细胞。Pdx1mRNA也被MET上调。 MET与激活素和碱性成纤维细胞生长因子协同作用对Pdx1表达细胞的增强作用。此外，MET刺激对晚期定形内胚层上调了热休克蛋白72，并激活了ES细胞中的各种激酶，包括Akt，细胞外信号调节激酶，p38和c-jun NH 2 末端激酶。结论我们的发现表明MET以时间依赖性方式诱导定形内胚层中Pdx1表达细胞的分化，并为再生医学提供了有用的应用。

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