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

34 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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DNA Methylation
Mesenchymal Stromal Cells
Epigenomics
Induced Pluripotent Stem Cells
Embryonic Stem Cells
Clone Cells
Tissue Donors
CpG Islands
Dermatoglyphics
Oligonucleotide Array Sequence Analysis
Methylation
Bone Marrow
Genes

Cite this

Shao, Kaifeng ; Koch, Carmen ; Gupta, Manoj K ; Lin, Qiong ; Lenz, Michael ; Laufs, Stephanie ; Denecke, Bernd ; Schmidt, Manfred ; Linke, Matthias ; Hennies, Hans C ; Hescheler, Jürgen ; Zenke, Martin ; Zechner, Ulrich ; Šarić, Tomo ; Wagner, Wolfgang. / Induced Pluripotent Mesenchymal Stromal Cell Clones Retain Donor-derived Differences in DNA Methylation Profiles. In: Molecular Therapy. 2013 ; Vol. 21, No. 1. pp. 240-250.
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Shao, K, Koch, C, Gupta, MK, Lin, Q, Lenz, M, Laufs, S, Denecke, B, Schmidt, M, Linke, M, Hennies, HC, Hescheler, J, Zenke, M, Zechner, U, Šarić, T & Wagner, W 2013, 'Induced Pluripotent Mesenchymal Stromal Cell Clones Retain Donor-derived Differences in DNA Methylation Profiles', Molecular Therapy, vol. 21, no. 1, pp. 240-250. https://doi.org/10.1038/mt.2012.207

Induced Pluripotent Mesenchymal Stromal Cell Clones Retain Donor-derived Differences in DNA Methylation Profiles. / Shao, Kaifeng; Koch, Carmen; Gupta, Manoj K; Lin, Qiong; Lenz, Michael; Laufs, Stephanie; Denecke, Bernd; Schmidt, Manfred; Linke, Matthias; Hennies, Hans C; Hescheler, Jürgen; Zenke, Martin; Zechner, Ulrich; Šarić, Tomo; Wagner, Wolfgang.

In: Molecular Therapy, Vol. 21, No. 1, 01.2013, p. 240-250.

Research output: Contribution to journalArticle

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T1 - Induced Pluripotent Mesenchymal Stromal Cell Clones Retain Donor-derived Differences in DNA Methylation Profiles

AU - Shao, Kaifeng

AU - Koch, Carmen

AU - Gupta, Manoj K

AU - Lin, Qiong

AU - Lenz, Michael

AU - Laufs, Stephanie

AU - Denecke, Bernd

AU - Schmidt, Manfred

AU - Linke, Matthias

AU - Hennies, Hans C

AU - Hescheler, Jürgen

AU - Zenke, Martin

AU - Zechner, Ulrich

AU - Šarić, Tomo

AU - Wagner, Wolfgang

PY - 2013/1

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N2 - 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.

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KW - Humans

KW - Immunohistochemistry

KW - Induced Pluripotent Stem Cells

KW - Mesenchymal Stromal Cells

KW - Reverse Transcriptase Polymerase Chain Reaction

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