Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts.
Differential methylation of tissue- and cancer-specific CpG island shores distinguishes human induced pluripotent stem cells, embryonic stem cells and fibroblasts.
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DOI：
10.1038/ng.471
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发表时间：
2009-12
期刊：
影响因子：
30.8
通讯作者：
Feinberg, Andrew P.
中科院分区：
文献类型：
--
作者：
Doi, Akiko;Park, In-Hyun;Wen, Bo;Murakami, Peter;Aryee, Martin J.;Irizarry, Rafael;Herb, Brian;Ladd-Acosta, Christine;Rho, Junsung;Loewer, Sabine;Miller, Justine;Schlaeger, Thorsten;Daley, George Q.;Feinberg, Andrew P.
诱导多能干细胞（iPS）是通过表观遗传重编程获得的，但其DNA甲基化模式尚未在全基因组范围内进行分析。在这里，我们发现大量的高甲基化和低甲基化的胞嘧啶磷酸鸟嘌呤（CpG）岛海岸在9个人类iPS细胞系相比，他们的父母成纤维细胞。重编程细胞中的差异甲基化区域（DMR）（表示为R-DMR）在组织特异性（T-DMR; 2.6倍，P < 10−4）和癌症特异性DMR（C-DMR; 3.6倍，P < 10−4）中显著富集。值得注意的是，即使iPS细胞来源于成纤维细胞，它们的R-DMR也可以区分正常的脑、肝和脾细胞以及结肠癌和正常结肠细胞。因此，许多DMR广泛参与组织分化、表观遗传重编程和癌症。我们观察到低甲基化的R-DMR与高甲基化的C-DMR和二价染色质标记的共定位，以及高甲基化的R-DMR与低甲基化的C-DMR的共定位和二价标记的缺失，这表明iPS细胞和癌症中表观遗传重编程的两种机制。
Induced pluripotent stem (iPS) cells are derived by epigenetic reprogramming, but their DNA methylation patterns have not yet been analyzed on a genome-wide scale. Here, we find substantial hypermethylation and hypomethylation of cytosine-phosphate-guanine (CpG) island shores in nine human iPS cell lines as compared to their parental fibroblasts. The differentially methylated regions (DMRs) in the reprogrammed cells (denoted R-DMRs) were significantly enriched in tissue-specific (T-DMRs; 2.6-fold, P < 10−4) and cancer-specific DMRs (C-DMRs; 3.6-fold, P < 10−4). Notably, even though the iPS cells are derived from fibroblasts, their R-DMRs can distinguish between normal brain, liver and spleen cells and between colon cancer and normal colon cells. Thus, many DMRs are broadly involved in tissue differentiation, epigenetic reprogramming and cancer. We observed colocalization of hypomethylated R-DMRs with hypermethylated C-DMRs and bivalent chromatin marks, and colocalization of hypermethylated R-DMRs with hypomethylated C-DMRs and the absence of bivalent marks, suggesting two mechanisms for epigenetic reprogramming in iPS cells and cancer.
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影响因子：
64.5
作者：
Park IH;Arora N;Huo H;Maherali N;Ahfeldt T;Shimamura A;Lensch MW;Cowan C;Hochedlinger K;Daley GQ
通讯作者：
Daley GQ
影响因子：
46.9
作者：
Deng, Jie;Shoemaker, Robert;Xie, Bin;Gore, Athurva;LeProust, Emily M.;Antosiewicz-Bourget, Jessica;Egli, Dieter;Maherali, Nimet;Park, In-Hyun;Yu, Junying;Daley, George Q.;Eggan, Kevin;Hochedlinger, Konrad;Thomson, James;Wang, Wei;Gao, Yuan;Zhang, Kun
通讯作者：
Zhang, Kun
影响因子：
64.8
作者：
Park, In-Hyun;Zhao, Rui;Daley, George Q.
通讯作者：
Daley, George Q.
影响因子：
64.5
作者：
Takahashi, Kazutoshi;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya
影响因子：
56.9
作者：
Yu, Junying;Vodyanik, Maxim A.;Thomson, James A.
通讯作者：
Thomson, James A.