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- W2336019559 abstract "Pancreatic and duodenal homeobox 1 (Pdx1) is a transcription factor that regulates the embryonic development of the pancreas and the differentiation toward β cells. Previously, we have shown that exposure of mouse embryonic stem cells (mESCs) to high concentrations of diethylenetriamine nitric oxide adduct (DETA-NO) triggers differentiation events and promotes the expression of Pdx1. Here we report evidence that Pdx1 expression is associated with release of polycomb repressive complex 2 (PRC2) and P300 from its promoter region. These events are accompanied by epigenetic changes in bivalent markers of histones trimethylated histone H3 lysine 27 (H3K27me3) and H3K4me3, site-specific changes in DNA methylation, and no change in H3 acetylation. On the basis of these findings, we developed a protocol to differentiate mESCs toward insulin-producing cells consisting of sequential exposure to DETA-NO, valproic acid, and P300 inhibitor (C646) to enhance Pdx1 expression and a final maturation step of culture in suspension to form cell aggregates. This small molecule-based protocol succeeds in obtaining cells that express pancreatic β-cell markers such as PDX1, INS1, GCK, and GLUT2 and respond in vitro to high glucose and KCl." @default.
- W2336019559 created "2016-06-24" @default.
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- W2336019559 date "2016-10-01" @default.
- W2336019559 modified "2023-10-16" @default.
- W2336019559 title "Differentiation of Mouse Embryonic Stem Cells toward Functional Pancreatic β-Cell Surrogates through Epigenetic Regulation of<i>Pdx1</i>by Nitric Oxide" @default.
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- W2336019559 doi "https://doi.org/10.3727/096368916x691178" @default.
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