DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells

被引：335

作者：

Bork, Simone ^{[2
,3
]}

Pfister, Stefan ^{[3
,4
]}

Witt, Hendrik ^{[4
]}

Horn, Patrick ^{[2
]}

Korn, Bernhard ^{[5
]}

Ho, Anthony D. ^{[2
,3
]}

Wagner, Wolfgang ^{[1
,2
,3
]}

机构：

[1] Univ Aachen, Sch Med, Helmholtz Inst Biomed Engn, D-52074 Aachen, Germany

[2] Heidelberg Univ, Dept Med 5, D-69120 Heidelberg, Germany

[3] Heidelberg Acad Sci & Humanities, D-69117 Heidelberg, Germany

[4] Heidelberg Univ, Dept Pediat Oncol Hematol & Immunol, D-69120 Heidelberg, Germany

[5] German Canc Res Ctr, Genom & Prote Core Facil, D-69120 Heidelberg, Germany

来源：

AGING CELL | 2010年 / 9卷 / 01期

关键词：

aging; DNA methylation; human mesenchymal stromal cells; long-term culture; pyrosequencing; senescence; HUMAN BONE-MARROW; STEM-CELLS; INTERNATIONAL-SOCIETY; LIFE-SPAN; GENE; SENESCENCE; EXPRESSION; CPG; PROMOTER; AGE;

D O I：

10.1111/j.1474-9726.2009.00535.x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

P>Within 2-3 months of in vitro culture-expansion, mesenchymal stromal cells (MSC) undergo replicative senescence characterized by cell enlargement, loss of differentiation potential and ultimate growth arrest. In this study, we have analyzed DNA methylation changes upon long-term culture of MSC by using the HumanMethylation27 BeadChip microarray assessing 27 578 unique CpG sites. Furthermore, we have compared MSC from young and elderly donors. Overall, methylation patterns were maintained throughout both long-term culture and aging but highly significant differences were observed at specific CpG sites. Many of these differences were observed in homeobox genes and genes involved in cell differentiation. Methylation changes were verified by pyrosequencing after bisulfite conversion and compared to gene expression data. Notably, methylation changes in MSC were overlapping in long-term culture and aging in vivo. This supports the notion that replicative senescence and aging represent developmental processes that are regulated by specific epigenetic modifications.

引用

页码：54 / 63

页数：10

共 55 条

[1] Proliferation kinetics and differentiation potential of ex vivo expanded human bone marrow stromal cells: Implications for their use in cell therapy [J].