Replicative senescence of mesenchymal stem cells causes DNA-methylation changes which correlate with repressive histone marks | Zendy

Anne Schellenberg | Zendy; Qiong Lin | Zendy; Herdit M. Schüler | Zendy; Carmen Koch | Zendy; Sylvia Joussen | Zendy; Bernd Denecke | Zendy; Gudrun Walenda | Zendy; Norbert Pallua | Zendy; Christoph V. Suschek | Zendy; Martin Zenke | Zendy; Wolfgang Wagner | Zendy

Open Access

Replicative senescence of mesenchymal stem cells causes DNA-methylation changes which correlate with repressive histone marks

Author(s) -

Anne Schellenberg,

Qiong Lin,

Herdit M. Schüler,

Carmen Koch,

Sylvia Joussen,

Bernd Denecke,

Gudrun Walenda,

Norbert Pallua,

Christoph V. Suschek,

Martin Zenke,

Wolfgang Wagner

Publication year - 2011

Publication title -

aging

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.473

H-Index - 90

ISSN - 1945-4589

DOI - 10.18632/aging.100391

Subject(s) - biology , senescence , histone , mesenchymal stem cell , microbiology and biotechnology , dna methylation , epigenetics , dna , genetics , gene , gene expression

Cells in culture undergo replicative senescence. In this study, we analyzed functional, genetic and epigenetic sequels of long-term culture in human mesenchymal stem cells (MSC). Already within early passages the fibroblastoid colony-forming unit (CFU-f) frequency and the differentiation potential of MSC declined significantly. Relevant chromosomal aberrations were not detected by karyotyping and SNP-microarrays. Subsequently, we have compared DNA-methylation profiles with the Infinium HumanMethylation27 Bead Array and the profiles differed markedly in MSC derived from adipose tissue and bone marrow. Notably, all MSC revealed highly consistent senescence-associated modifications at specific CpG sites. These DNA-methylation changes correlated with histone marks of previously published data sets, such as trimethylation of H3K9, H3K27 and EZH2 targets. Taken together, culture expansion of MSC has profound functional implications - these are hardly reflected by genomic instability but they are associated with highly reproducible DNA-methylation changes which correlate with repressive histone marks. Therefore replicative senescence seems to be epigenetically controlled.

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