Drawing a differentiation potency index of iPSC based on genomic imprinting

为了从基因组印记的角度评价iPSC，我们分析了小鼠成纤维细胞、正常人和Beckwith-Wiedemann综合征患者外周血细胞来源的iPSC中分散在基因组中的印记相关差异甲基化区域（DMR）的DNA甲基化状态。我们还分析了肝母细胞瘤，它起源于未成熟的肝脏前体细胞。我们发现，在小鼠iPSC中，许多DMR的甲基化状态在重编程后降低，并且在视黄酸诱导分化期间，一定数量的DMR恢复了它们的甲基化状态。人类iPSC显示，在重编程后，几种DMR的甲基化模式变为父系表观基因型。最后，肝母细胞瘤分析表明，在肿瘤发展之前，在一些DMR中发生低甲基化。

To evaluate iPSC from the aspect of genomic imprinting, we analyzed DNA methylation status of imprinting related differentially methylated regions (DMRs), which were scattered throughout the genome, in iPSCs derived from mouse fibroblast, peripheral blood cells of normal human and Beckwith-Wiedemann syndrome patients. We also analyzed hepatoblastomas, which originated from immature liver precursor cells. We found that in mouse iPSC, the methylation status of many DMRs decreased after reprogramming and that a certain number of DMRs restored their methylation status during retinoic acid induced differentiation. Human iPSC showed that methylation patterns of several DMRs changed to paternal epigenotype after reprogramming. Finally, hepatoblastoma analysis suggested that the occurrence of hypomethylation at a few DMRs prior to tumor development.