丙戊酸启动人导管腺癌细胞系Panc-1向α样细胞的转分化。

S. F. Petry, Naga Deepa Kandula, S. Günther, Christian S. M. Helker, U. Schagdarsurengin, T. Linn
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引用次数: 0

摘要

非间充质胰腺细胞是细胞替代的潜在来源。它们的转分化可以通过触发表观遗传重塑来实现。组蛋白的翻译后修饰。丙戊酸是一种支链饱和脂肪酸,具有组蛋白去乙酰化酶抑制剂活性,与胰腺上皮细胞中关键转录因子的表达和胰岛素转录有关。然而,丙戊酸引起细胞重编程的潜力尚未完全了解。为了进一步阐明这一点,我们采用了下一代RNA测序、实时PCR、ELISA和western blot蛋白分析来评估丙戊酸对panc -1细胞转录组和功能的影响。我们的研究结果表明,丙戊酸对细胞周期、细胞粘附、组蛋白H3乙酰化和代谢途径有显著影响,并通过组蛋白H3乙酰化引发上皮-间质转化,从而产生α-细胞样特征。我们的结论是,人胰腺上皮细胞可以通过丙戊酸的表观遗传调控转化为具有内分泌特性的细胞,有利于α-细胞样表型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Valproic Acid Initiates Transdifferentiation of the Human Ductal Adenocarcinoma Cell-line Panc-1 Into α-Like Cells.
Non-mesenchymal pancreatic cells are a potential source for cell replacement. Their transdifferentiation can be achieved by triggering epigenetic remodeling through e. g. post-translational modification of histones. Valproic acid, a branched-chain saturated fatty acid with histone deacetylase inhibitor activity, was linked to the expression of key transcription factors of pancreatic lineage in epithelial cells and insulin transcription. However, the potential of valproic acid to cause cellular reprogramming is not fully understood. To shed further light on it we employed next-generation RNA sequencing, real-time PCR, and protein analyses by ELISA and western blot, to assess the impact of valproic acid on transcriptome and function of Panc-1-cells. Our results indicate that valproic acid has a significant impact on the cell cycle, cell adhesion, histone H3 acetylation, and metabolic pathways as well as the initiation of epithelial-mesenchymal transition through acetylation of histone H3 resulting in α-cell-like characteristics. We conclude that human epithelial pancreatic cells can be transdifferentiated into cells with endocrine properties through epigenetic regulation by valproic acid favoring an α-cell-like phenotype.
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