Journal
MOLECULAR THERAPY
Volume 21, Issue 1, Pages 240-250Publisher
CELL PRESS
DOI: 10.1038/mt.2012.207
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Funding
- excellence initiative of the German federal government of the Faculty of Medicine, RWTH Aachen
- excellence initiative of the German state government of the Faculty of Medicine, RWTH Aachen
- state North-Rhine Westphalia within the BioNRW2 project StemCellFactory
- Stem Cell Network of North-Rhine Westphalia
- Koln Fortune Program
- German Research Foundation DFG [SPP1356]
- Federal Ministry for Education and Research
- Else-Kroner Fresenius Stiftung
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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 finger-prints 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. Received 30 January 2012; accepted 5 September 2012; advance online publication 2 October 2012. doi:10.1038/mt.2012.207
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