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Stem Cell Reports. 2013 Dec 26;2(1):36-43. doi: 10.1016/j.stemcr.2013.11.003. eCollection 2014 Jan 14.

A panel of CpG methylation sites distinguishes human embryonic stem cells and induced pluripotent stem cells.

Author information

1
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.
2
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.
3
Illumina, Inc., 9885 Towne Centre Drive, San Diego, CA 92121, USA.
4
Stem Cell Program in Institute for Cell Engineering and Division of Hematology, Johns Hopkins University, Baltimore, MD 21205, USA.
5
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 25 Orde Street, 5-1015-3 Toronto, Ontario, Canada M5T 3H7.
6
Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.

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.

PMID:
24511466
PMCID:
PMC3916755
DOI:
10.1016/j.stemcr.2013.11.003
[Indexed for MEDLINE]
Free PMC Article

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