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Inference of Specific Gene Regulation by Environmental Chemicals in Human Embryonic Stem Cells

机译:环境化学物质在人类胚胎干细胞中特定基因调控的推论

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We are exposed to many environmental chemicals in our daily life. Certain chemicals threaten our health, especially that of embryos and can cause serious developmental problems. To prevent abnormal development and diseases caused by chemicals, it is important to clarify the mechanisms of chemical toxicity in embryonic cells. The gene regulatory network is one of the useful methods for clarifying functional mechanisms in living cells, so we applied a statistical method to infer the gene regulatory network in human embryonic stem cells. In this study, we improved our previously developed SEM approach for inferring a network model from 9 gene expression profiles in human embryonic stem cells, which were exposed to various chemicals. The estimated regulatory models clarified the differences between chemicals, and the shapes of the inferred models reflected the features of the chemical toxicities. The toxicity of acrylamide affected neuronal cell-related genes, while that of diethylnitrosamine disturbed cell differentiation-related genes. On the other hand, the TCDD network reflected feedback regulation, and finally disturbed neuronal cell-related genes. In the Thalidomide network, cell differentiation genes related to axis formation in embyronic cells were affected by thalidomide toxicity.
机译:我们在日常生活中接触许多环境化学物质。某些化学物质会威胁我们的健康,尤其是胚胎的健康,并可能导致严重的发育问题。为了防止由化学物质引起的异常发育和疾病,阐明胚胎细胞化学毒性的机制非常重要。基因调控网络是阐明活细胞功能机制的有用方法之一,因此我们应用统计学方法推断人类胚胎干细胞中的基因调控网络。在这项研究中,我们改进了先前开发的SEM方法,以从人类胚胎干细胞(暴露于各种化学物质)中的9个基因表达谱推断网络模型。估计的监管模型澄清了化学物质之间的差异,推断模型的形状反映了化学毒性的特征。丙烯酰胺的毒性影响神经元细胞相关基因,而二乙基亚硝胺的毒性影响细胞分化相关基因。另一方面,TCDD网络反映了反馈调节,并最终扰乱了神经元细胞相关基因。在Thalidomide网络中,沙利度胺毒性影响与胚胎细胞轴形成有关的细胞分化基因。

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