Faculty of Science, Biology Department, Molecular Biology Section, Istanbul University, Vezneciler 34134, Istanbul, Turkey.
J Cell Biochem. 2018 Jan;119(1):455-467. doi: 10.1002/jcb.26203. Epub 2017 Jun 30.
In this study, we aimed to research the effects of class-I HDACs and glucose on differentiation of pancreatic islet derived mesenchymal stem cells (PI-MSCs) to beta cells. Beta cell differentiation determined by flow cytometric analysis and gene expression levels of PDX1, PAX4, PAX6, NKX6.1, NGN3, INS2, and GLUT2. As a result the valproic acid, is an inhibitor of class-I HDACs, caused the highest beta cell differentiation in PI-MSCs. However, the cells in this group were at early stages of differentiation. Glucose co-administration to this group carried the differentiation to higher levels, but these newly formed beta cells were not functional. Moreover, reduction in the levels of pluripotency factors that Oct3/4, c-Myc, and Nanog were parallel to beta cell differentiation. Also, the levels of HDAC1 and acetylated H3/H4 were increased and methylated H3 was decreased by VPA treatment. In addition, we have detected over expression in genes of miR-18a-5p, miR-19b-5p, miR-30d-3p, miR-124, miR-146a-5p, miR-184, miR-335, and miR-433-5p in parallel to beta cell differentiation. As the conclusion, this study is important for understanding the epigenetic mechanism that controls the beta cell differentation and it suggests new molecules that can be used for diagnosis, and treatment of diabetes. J. Cell. Biochem. 119: 455-467, 2018. © 2017 Wiley Periodicals, Inc.
在这项研究中，我们旨在研究 I 类组蛋白去乙酰化酶和葡萄糖对胰岛衍生间充质干细胞（PI-MSCs）向β细胞分化的影响。β细胞分化通过流式细胞术分析和 PDX1、PAX4、PAX6、NKX6.1、NGN3、INS2 和 GLUT2 的基因表达水平来确定。结果表明，丙戊酸是 I 类组蛋白去乙酰化酶的抑制剂，可使 PI-MSCs 中β细胞分化率达到最高。然而，该组细胞处于分化的早期阶段。将葡萄糖共给药至该组可使分化达到更高水平，但这些新形成的β细胞没有功能。此外，多能性因子 Oct3/4、c-Myc 和 Nanog 的水平降低与β细胞分化平行。此外，VPA 处理可增加 HDAC1 和乙酰化 H3/H4 的水平，并降低 H3 的甲基化水平。此外，我们还检测到 miR-18a-5p、miR-19b-5p、miR-30d-3p、miR-124、miR-146a-5p、miR-184、miR-335 和 miR-433-5p 的基因表达水平在与β细胞分化平行的情况下过表达。综上所述，这项研究对于了解控制β细胞分化的表观遗传机制非常重要，并为糖尿病的诊断和治疗提供了新的分子靶点。J. Cell. Biochem. 119: 455-467, 2018. © 2017 Wiley Periodicals, Inc.
