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

Kevin Huang; Yin Shen; Zhigang Xue; Marina Bibikova; Craig April; Zhenshan Liu; Linzhao Cheng; Andras Nagy; Matteo Pellegrini; Jian-Bing Fan; Guoping Fan

doi:10.1016/j.stemcr.2013.11.003

Stem Cell Reports (Jan 2014)

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

Kevin Huang,
Yin Shen,
Zhigang Xue,
Marina Bibikova,
Craig April,
Zhenshan Liu,
Linzhao Cheng,
Andras Nagy,
Matteo Pellegrini,
Jian-Bing Fan,
Guoping Fan

Affiliations

Kevin Huang: 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
Yin Shen: 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
Zhigang Xue: 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
Marina Bibikova: Illumina, Inc., 9885 Towne Centre Drive, San Diego, CA 92121, USA
Craig April: Illumina, Inc., 9885 Towne Centre Drive, San Diego, CA 92121, USA
Zhenshan Liu: 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
Linzhao Cheng: Stem Cell Program in Institute for Cell Engineering and Division of Hematology, Johns Hopkins University, Baltimore, MD 21205, USA
Andras Nagy: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 25 Orde Street, 5-1015-3 Toronto, Ontario, Canada M5T 3H7
Matteo Pellegrini: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA
Jian-Bing Fan: Illumina, Inc., 9885 Towne Centre Drive, San Diego, CA 92121, USA
Guoping Fan: 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

DOI: https://doi.org/10.1016/j.stemcr.2013.11.003
Journal volume & issue: Vol. 2, no. 1
pp. 36 – 43

Abstract

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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.

Published in Stem Cell Reports

ISSN: 2213-6711 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General)
Website: http://www.cell.com/stem-cell-reports/home

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