Genome-wide DNA methylation analysis reveals that mouse chemical iPSCs have closer epigenetic features to mESCs than OSKM-integrated iPSCs.
Genome-wide DNA methylation analysis reveals that mouse chemical iPSCs have closer epigenetic features to mESCs than OSKM-integrated iPSCs.
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全基因组 DNA 甲基化分析表明，与 OSKM 整合的 iPSC 相比，小鼠化学 iPSC 与 mESC 具有更接近的表观遗传特征
DOI：
10.1038/s41419-017-0234-x
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发表时间：
2018-02-07
影响因子：
9
通讯作者：
Yao H
中科院分区：
文献类型：
--
作者：
Ping W;Hu J;Hu G;Song Y;Xia Q;Yao M;Gong S;Jiang C;Yao H
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分化而来。化学IPSCs(C-IPSCs)和OSKM-IPSCs(4F-iPSCs)与小鼠胚胎干细胞(MESCs)具有相似的特性。然而，它们在表观遗传学上的等价性在整个基因组中仍然没有完全被理解。在本研究中，我们制备了小鼠C-iPSCs和4F-iPSCs，并进一步比较了C-iPSCs、4F-iPSCs和mESCs在2I和LIF中保持的全基因组DNA甲基组。三个多能干细胞总体上倾向于低甲基化，然而，某些特定区域(如反转录转座子)的DNA甲基化是细胞类型特有的。重要的是，C-iPSCs比4F-iPSCs的甲基化程度更低。亚硫酸氢盐测序表明，C-iPSCs中已知的Dlk1-Dio3和Peg12-Ube3a等印迹簇的DNA甲基化状态更接近mESCs，而不是4F-iPSCs。总体而言，我们的数据证明了C-iPSCs和4F-iPSCs的重编程方法依赖的表观遗传学差异，并揭示了C-iPSCs比OSKM整合的IPSCs更低甲基化。
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-Dio3andPeg12-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.
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影响因子：
12.3
作者：
Heyn H;Vidal E;Ferreira HJ;Vizoso M;Sayols S;Gomez A;Moran S;Boque-Sastre R;Guil S;Martinez-Cardus A;Lin CY;Royo R;Sanchez-Mut JV;Martinez R;Gut M;Torrents D;Orozco M;Gut I;Young RA;Esteller M
通讯作者：
Esteller M
转座元件位于胚胎发生、胚胎干细胞、重编程和长非编码RNA之间十字路口的中心
影响因子：
18.9
作者：
Hutchins AP;Pei D
通讯作者：
Pei D
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
64.5
作者：
Dowen JM;Fan ZP;Hnisz D;Ren G;Abraham BJ;Zhang LN;Weintraub AS;Schujiers J;Lee TI;Zhao K;Young RA
通讯作者：
Young RA
影响因子：
1.2
作者：
Burnett LC;LeDuc CA;Sulsona CR;Paull D;Eddiry S;Levy B;Salles JP;Tauber M;Driscoll DJ;Egli D;Leibel RL
通讯作者：
Leibel RL