title: Induced pluripotent mesenchymal stromal cell clones retain donor-derived differences in DNA methylation profiles.
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.
authors.affiliation: Institute for Neurophysiology, Medical Center, University of Cologne, Cologne, Germany.
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Shao
authors.forename: Carmen
authors.initials: C
authors.lastname: Koch
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Gupta
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lin
authors.forename: Michael
authors.initials: M
authors.lastname: Lenz
authors.forename: Stephanie
authors.initials: S
authors.lastname: Laufs
authors.forename: Bernd
authors.initials: B
authors.lastname: Denecke
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmidt
authors.forename: Matthias
authors.initials: M
authors.lastname: Linke
authors.forename: Hans C
authors.initials: HC
authors.lastname: Hennies
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hescheler
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zechner
authors.forename: Tomo
authors.initials: T
authors.lastname: Šarić
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wagner
mesh_terms: D002999:Clone Cells; D018899:CpG Islands; D019175:DNA Methylation; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction