title: A panel of CpG methylation sites distinguishes human embryonic stem cells and induced pluripotent stem cells.
abstract: 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.
authors: Department of Human Genetics, Broad Stem Cell Research Center, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles Young Drive, Los Angeles, CA 90095, USA.
authors: Kevin
authors: K
authors: Huang
authors: Department of Human Genetics, Broad Stem Cell Research Center, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles Young Drive, Los Angeles, CA 90095, USA.
authors: Yin
authors: Y
authors: Shen
authors: Department of Human Genetics, Broad Stem Cell Research Center, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles Young Drive, Los Angeles, CA 90095, USA ; Translational Stem Cell Center, Tongji Hospital and Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai 200092, China.
authors: Zhigang
authors: Z
authors: Xue
authors: Illumina, Inc., 9885 Towne Centre Drive, San Diego, CA 92121, USA.
authors: Marina
authors: M
authors: Bibikova
authors: Illumina, Inc., 9885 Towne Centre Drive, San Diego, CA 92121, USA.
authors: Craig
authors: C
authors: April
authors: Department of Human Genetics, Broad Stem Cell Research Center, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles Young Drive, Los Angeles, CA 90095, USA ; Translational Stem Cell Center, Tongji Hospital and Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai 200092, China.
authors: Zhenshan
authors: Z
authors: Liu
authors: Stem Cell Program in Institute for Cell Engineering and Division of Hematology, Johns Hopkins University, Baltimore, MD 21205, USA.
authors: Linzhao
authors: L
authors: Cheng
authors: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 25 Orde Street, 5-1015-3 Toronto, Ontario, Canada M5T 3H7.
authors: Andras
authors: A
authors: Nagy
authors: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Matteo
authors: M
authors: Pellegrini
authors: Illumina, Inc., 9885 Towne Centre Drive, San Diego, CA 92121, USA.
authors: Jian-Bing
authors: JB
authors: Fan
authors: Department of Human Genetics, Broad Stem Cell Research Center, David Geffen School of Medicine, University of California, Los Angeles, 695 Charles Young Drive, Los Angeles, CA 90095, USA.
authors: Guoping
authors: G
authors: Fan
mesh_terms: D002478:Cells, Cultured; D018899:CpG Islands; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D060388:Support Vector Machine; D059467:Transcriptome; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D000097584:DNA Methyltransferase 3B