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首页> 外文期刊>Balkan journal of medical genetics: BJMG >Effect of exogenous transcription factors integration sites on safety and pluripotency of induced pluripotent stem cells
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Effect of exogenous transcription factors integration sites on safety and pluripotency of induced pluripotent stem cells

机译：外源转录因子集成位点对诱导多能干细胞安全性和多能性的影响

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Induced pluripotent stem cells (iPSCs), generated from somatic cells, not only possess similar characteristics with embryonic stem cells (ESCs), but also present more advantages than ESCs in medical applications. The classical induction method that utilizes the integration of exogenous genes into chromosomes may raise the potential risk of the safety of iPSCs. To investigate the potential correlation between the integration sites of exogenous transcription factors (TFs) and iPSCsa?? pluripotency and safety, the integration of exogenous genes in three iPSC lines, which met the golden standard of murine developmental assay (tetraploid complementation), were analyzed. Twenty-two integration sites of exogenous TFs were identified by nested inverse polymerase chain reaction (iPCR) and 39 flanking genesa?? functions were analyzed by gene ontology (GO). In the 22 integrated sites, 17 (77.3%) were located in the intergenic regions and the remainder were located in introns far from the transcription start sites. Microarray analysis of the flanking genes in these cells showed that there was no distinct difference in expression levels between the iPSCs, ESCs and mouse embryonic fibroblast (MEF), suggesting that the integration of exogenous TFs has no significant influence on the expression of flanking genes. Gene ontology analysis showed that although most of the flanking genes were housekeeping genes, which were necessary for basic life activity, none of these 39 flanking genes have correlation with tumorigenesis or embryogenesis, suggesting that the integration sites hold low risk of tumorigenesis.
机译：从体细胞产生的诱导多能干细胞（IPSC），不仅具有与胚胎干细胞（ESC）的类似特征，而且还具有比医学应用中的ESC的更优点。使用外源基因的经典诱导方法可以提高IPSCS安全的潜在风险。探讨外源转录因子（TFS）和IPSCSA之间的集成位点之间的潜在相关性吗？分析了多能性和安全性，分析了三种IPSC线中的外源基因的整合，其符合鼠发育测定（四倍体互补）的黄金标准。通过嵌套的反相聚合酶链反应（IPCR）和39个侧翼基因鉴定外源TFS的二十二个整体部位。通过基因本体进行分析功能（GO）。在22个综合网站中，17个（77.3％）位于非基因区域，其余部分位于远离转录起始位点的内含子中。这些细胞中的侧翼基因的微阵列分析表明，IPSC，ESC和小鼠胚胎成纤维细胞（MEF）之间的表达水平没有明显差异，表明外源TFS的整合对侧翼基因的表达没有显着影响。基因本体分析表明，尽管大多数侧翼基因是管家基因，但碱性生命活动所需的是，这39个侧翼基因中的任何一个都没有与肿瘤发生或胚胎发生相关，这表明整合位点具有低风险的肿瘤发生。

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