Induced Pluripotent Mesenchymal Stromal Cell Clones Retain Donor-derived Differences in DNA Methylation Profiles

Kaifeng Shao, Carmen Koch, Manoj K Gupta, Qiong Lin, Michael Lenz, Stephanie Laufs, Bernd Denecke, Manfred Schmidt, Matthias Linke, Hans C Hennies, Jürgen Hescheler, Martin Zenke, Ulrich Zechner, Tomo Šarić, Wolfgang Wagner

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is an epigenetic phenomenon. It has been suggested that iPSC retain some tissue-specific memory whereas little is known about interindividual epigenetic variation. We have reprogrammed mesenchymal stromal cells from human bone marrow (iP-MSC) and compared their DNA methylation profiles with initial MSC and embryonic stem cells (ESCs) using high-density DNA methylation arrays covering more than 450,000 CpG sites. Overall, DNA methylation patterns of iP-MSC and ESC were similar whereas some CpG sites revealed highly significant differences, which were not related to parental MSC. Furthermore, hypermethylation in iP-MSC versus ESC occurred preferentially outside of CpG islands and was enriched in genes involved in epidermal differentiation indicating that these differences are not due to random de novo methylation. Subsequently, we searched for CpG sites with donor-specific variation. These "epigenetic fingerprints" were highly enriched in non-promoter regions and outside of CpG islands-and they were maintained upon reprogramming. In conclusion, iP-MSC clones revealed relatively little intraindividual variation but they maintained donor-derived epigenetic differences. In the absence of isogenic controls, it would therefore be more appropriate to compare iPSC from different donors rather than a high number of different clones from the same patient.

Original languageEnglish
Pages (from-to)240-250
Number of pages11
JournalMolecular Therapy
Volume21
Issue number1
DOIs
Publication statusPublished - Jan 2013
Externally publishedYes

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