CAS Key Laboratory of Regenerative Biology, Joint School of Life Sciences, CAS Center for Excellence in Molecular Cell Science, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou, China.
Institute of Health Sciences, Anhui University, Hefei, China.
Cell Death Dis. 2018 Feb 7;9(2):187. doi: 10.1038/s41419-017-0234-x.
Induced pluripotent stem cells can be derived from somatic cells through ectopic expression of transcription factors or chemical cocktails. Chemical iPSCs (C-iPSCs) and OSKM-iPSCs (4F-iPSCs) have been suggested to have similar characteristics to mouse embryonic stem cells (mESCs). However, their epigenetic equivalence remains incompletely understood throughout the genome. In this study, we have generated mouse C-iPSCs and 4F-iPSCs, and further compared the genome-wide DNA methylomes of C-iPSCs, 4F-iPSCs, and mESCs that were maintained in 2i and LIF. Three pluripotent stem cells tend to be low methylated overall, however, DNA methylations in some specific regions (such as retrotransposons) are cell type-specific. Importantly, C-iPSCs are more hypomethylated than 4F-iPSCs. Bisulfite sequencing indicated that DNA methylation status in several known imprinted clusters, such as: Dlk1-Dio3 and Peg12-Ube3a, in C-iPSCs are closer to those of mESCs than 4F-iPSCs. Overall, our data demonstrate the reprogramming methods-dependent epigenetic differences of C-iPSCs and 4F-iPSCs and reveal that C-iPSCs are more hypomethylated than OSKM-integrated iPSCs.
诱导多能干细胞可以通过异位表达转录因子或化学鸡尾酒从体细胞中获得。化学诱导多能干细胞（C-iPSCs）和 OSKM-iPSCs（4F-iPSCs）被认为具有类似于小鼠胚胎干细胞（mESCs）的特征。然而，它们在整个基因组中的表观遗传等效性仍不完全清楚。在这项研究中，我们生成了小鼠 C-iPSCs 和 4F-iPSCs，并进一步比较了在 2i 和 LIF 中维持的 C-iPSCs、4F-iPSCs 和 mESCs 的全基因组 DNA 甲基组。三种多能干细胞总体上倾向于低甲基化，但一些特定区域（如反转录转座子）的 DNA 甲基化是细胞类型特异性的。重要的是，C-iPSCs 比 4F-iPSCs 更低甲基化。亚硫酸氢盐测序表明，C-iPSCs 中几个已知印迹簇（如 Dlk1-Dio3 和 Peg12-Ube3a）的 DNA 甲基化状态比 4F-iPSCs 更接近 mESCs。总体而言，我们的数据表明 C-iPSCs 和 4F-iPSCs 的重编程方法依赖性的表观遗传差异，并揭示 C-iPSCs 比 OSKM 整合的 iPSCs 更低甲基化。
