A Panel of CpG Methylation Sites Distinguishes Human Embryonic Stem Cells and Induced Pluripotent Stem Cells

被引:36
作者
Huang, Kevin [1 ]
Shen, Yin [1 ]
Xue, Zhigang [1 ,3 ,4 ]
Bibikova, Marina [2 ]
April, Craig [2 ]
Liu, Zhenshan [1 ,3 ,4 ]
Cheng, Linzhao [6 ,7 ]
Nagy, Andras [8 ]
Pellegrini, Matteo [5 ]
Fan, Jian-Bing [2 ]
Fan, Guoping [1 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Broad Stem Cell Res Ctr, Dept Human Genet, Los Angeles, CA 90095 USA
[2] Illumina Inc, San Diego, CA 92121 USA
[3] Tongji Univ, Sch Med, Tongji Hosp, Translat Stem Cell Ctr, Shanghai 200092, Peoples R China
[4] Tongji Univ, Sch Med, Dept Regenerat Med, Shanghai 200092, Peoples R China
[5] Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA 90095 USA
[6] Johns Hopkins Univ, Inst Cell Engn, Stem Cell Program, Baltimore, MD 21205 USA
[7] Johns Hopkins Univ, Div Hematol, Baltimore, MD 21205 USA
[8] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5T 3H7, Canada
关键词
GENE-EXPRESSION SIGNATURES; DNA METHYLATION; METHYLOME; MEMORY; MOUSE;
D O I
10.1016/j.stemcr.2013.11.003
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Whether human induced pluripotent stem cells (hiPSCs) are epigenetically identical to human embryonic stem cells (hESCs) has been debated in the stem cell field. In this study, we analyzed DNA methylation patterns in a large number of hiPSCs (n = 114) and hESCs (n = 155), and identified a panel of 82 CpG methylation sites that can distinguish hiPSCs from hESCs with high accuracy. We show that 12 out of the 82 CpG sites were subject to hypermethylation in part by DNMT3B. Notably, DNMT3B contributes directly to aberrant hypermethylation and silencing of the signature gene, TCERG1L. Overall, we conclude that DNMT3B is involved in a wave of de novo methylation during reprogramming, a portion of which contributes to the unique hiPSC methylation signature. These 82 CpG methylation sites may be useful as biomarkers to distinguish between hiPSCs and hESCs.
引用
收藏
页码:36 / 43
页数:8
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