Aberrant DNA methylation reprogramming during iPS cell generation is dependent on the choice of reprogramming factors

we generate iPSCs from a common fibroblast cell source using either the Yamanaka factors (OCT4, SOX2, KLF4 and MYC) or the Thomson factors (OCT4, SOX2, NANOG and LIN28) and determined their genome-wide DNA methylation profiles. In addition to shared DNA methylation aberrations present in all our iPSCs, we identify Yamanaka-iPSC (Y-iPSCs)-specific and Thomson-iPSCs (T-iPSC)-specific recurrent aberrations. Bisulphite converted DNA from 9 iPS cells derived using Yamanaka factors (OSKM), 6 iPS cells derived using Thompson factors (OSLN), 2 parental fibroblasts and one embrionic ES cell were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

本研究以普通成纤维细胞为细胞来源，分别采用山中伸弥因子（Yamanaka factors，包含OCT4、SOX2、KLF4及MYC）或汤姆森因子（Thomson factors，包含OCT4、SOX2、NANOG及LIN28）诱导生成诱导多能干细胞（induced pluripotent stem cells, iPSCs），并对其全基因组DNA甲基化谱进行了检测。除所有iPSCs共有的DNA甲基化异常外，本研究还鉴定出了山中伸弥诱导iPSC（Y-iPSCs）与汤普森诱导iPSC（T-iPSCs）特异性的复发性DNA甲基化异常。本研究将来自9株经山中伸弥因子（OSKM）诱导的iPSC、6株经汤普森因子（OSLN）诱导的iPSC、2株亲本成纤维细胞以及1株胚胎干细胞的亚硫酸氢盐转化DNA，与Illumina Infinium 450K人类甲基化芯片进行了杂交。