Article

Recurrent variations in DNA methylation in human pluripotent stem cells and their differentiated derivatives.

Center for Regenerative Medicine, Department of Chemical Physiology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Cell stem cell (Impact Factor: 22.15). 05/2012; 10(5):620-34. DOI: 10.1016/j.stem.2012.02.013
Source: PubMed

ABSTRACT Human pluripotent stem cells (hPSCs) are potential sources of cells for modeling disease and development, drug discovery, and regenerative medicine. However, it is important to identify factors that may impact the utility of hPSCs for these applications. In an unbiased analysis of 205 hPSC and 130 somatic samples, we identified hPSC-specific epigenetic and transcriptional aberrations in genes subject to X chromosome inactivation (XCI) and genomic imprinting, which were not corrected during directed differentiation. We also found that specific tissue types were distinguished by unique patterns of DNA hypomethylation, which were recapitulated by DNA demethylation during in vitro directed differentiation. Our results suggest that verification of baseline epigenetic status is critical for hPSC-based disease models in which the observed phenotype depends on proper XCI or imprinting and that tissue-specific DNA methylation patterns can be accurately modeled during directed differentiation of hPSCs, even in the presence of variations in XCI or imprinting.

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Available from: Jeanne F Loring, Jul 02, 2015
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Questions & Answers about this publication

  • Jeanne F Loring added an answer in DNA Methylation:
    The Cancer Genome Atlas (TCGA) and Illumina Human Methylation CpG Island Identifiers
    I am examining the TCGA Methylation (Glioblastoma multiforme) dataset, to assess whether we can use it as a means for identification of potential biomarkers for clinical development. The issue I have is that we, ourselves, don't (at least yet) run our own chips here, nor have we done any Illumina assay chip designs.

    Is there a readily-available public reference-list database that I've missed, which will allow me to bridge from the Illumina Human Methylation 27/450 CG# identifier codes back to standard NCBI Gene/RefSeq? I recall that, in the early days of TaqMan assay development, the exact targets of the SNP assays were all proprietary, and the marriage of those assays to Illumina sequence identifiers was sometimes challenging, if one needed to identify actual targets to assess biological plausibility/relevance...
    Jeanne F Loring · The Scripps Research Institute
    If you're interested in a non-cancer dataset, we have Illumina gene expression array data and 450K methylation data linked in our paper on human pluripotent stem cells: