Mild electrical stimulation with heat shock guides differentiation of embryonic stem cells into Pdx1-expressing cells within the definitive endoderm.
Mild electrical stimulation with heat shock guides differentiation of embryonic stem cells into Pdx1-expressing cells within the definitive endoderm.
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DOI：
10.1186/s12896-017-0331-z
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发表时间：
2017-02-15
影响因子：
3.5
通讯作者：
Kai H
中科院分区：
文献类型：
--
作者：
Koga T;Shiraki N;Yano S;Suico MA;Morino-Koga S;Sato T;Shuto T;Kume S;Kai H
由于糖尿病患者数量的增加，重要的是产生胰腺和十二指肠同源盒基因1（Pdx 1）表达细胞，其能够分化为胰腺内分泌β细胞。据报道，温和的电刺激可调节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肌细胞。在这项研究中，我们报告说，温和的电刺激与热休克（MET）加强分化的ES细胞成定形内胚层来源的Pdx 1表达细胞。当在分化第5天应用于早期定形内胚层时，MET没有影响。当在分化第7天Pdx 1/GFP表达细胞浸没前一天对晚期定形内胚层施加刺激时，观察到Pdx 1表达细胞的比例增加1.87倍。MET可上调Pdx 1 mRNA表达。MET的增强作用与激活素和碱性成纤维细胞生长因子协同进入Pdx 1表达细胞。此外，MET对晚期定形内胚层的刺激上调了ES细胞中的热休克蛋白72并激活了多种激酶，包括Akt、细胞外信号调节激酶、p38和c-jun NH 2-末端激酶。我们的研究结果表明，MET诱导分化的Pdx 1表达细胞内的定形内胚层在一个时间依赖性的方式，并建议再生医学的有用的应用。本文的在线版本（doi：10.1186/s12896-017-0331-z）包含补充材料，可供授权用户使用。
Because 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. In 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. Our 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. The online version of this article (doi:10.1186/s12896-017-0331-z) contains supplementary material, which is available to authorized users.