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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2012.1
- 수록면
- 503 - 512 (10page)
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초록· 키워드
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Human bone marrow mesenchymal stem cells (MSCs)expanded in vitro exhibit not only a tendency to lose their proliferative potential, homing ability and telomere length but also genetic or epigenetic modifications,resulting in senescence. We compared differential methylation patterns of genes and miRNAs between early-passage [passage 5 (P5)] and late-passage (P15) cells and estimated the relationship between senescence and DNA methylation patterns. When we examined hypermethylated genes (methylation peak ≥ 2) at P5 or P15, 2,739 genes, including those related to fructose and mannose metabolism and calcium signaling pathways, and 2,587 genes, including those related to DNA replication, cell cycle and the PPAR signaling pathway, were hypermethylated at P5and P15, respectively. There was common hypermethylation of 1,205 genes at both P5 and P15. In addition,genes that were hypermethylated at P5 (CPEB1,GMPPA, CDKN1A, TBX2, SMAD9 and MCM2) showed lower mRNA expression than did those hypermethylated at P15, whereas genes that were hypermethylated at P15 (MAML2, FEN1 and CDK4) showed lower mRNA expression than did those that were hypermethylated at P5, demonstrating that hypermethylation at DNA promoter regions inhibited gene expression and that hypomethylation increased gene expression. In the case of hypermethylation on miRNA,27 miRNAs were hypermethylated at P5, whereas 44miRNAs were hypermethylated at P15. These results show that hypermethylation increases at genes related to DNA replication, cell cycle and adipogenic differentiation due to long-term culture, which may in part affect MSC senescence.
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참고문헌 (25)
참고문헌 신청
Antequera F / 2003 / Structure, function and evolution of CpG island promoters / Cell Mol Life Sci 60 : 1647 ~ 1658
Banfi A / 2000 / Proliferation kinetics and differentiation potential of ex vivo expanded human bone marrow stromal cells: Implications for their use in cell therapy / Exp He
Baxter MA / 2004 / Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion / Stem Cells 22 : 675 ~ 682
Beausejour CM / 2003 / Reversal of human cellular senescence: roles of the p53 and p16 pathways / EMBO J 22 : 4212 ~ 4222
Benjamini Y / 1995 / Controlling the false discovery rate: a practical and powerful approach to multiple testing / J R Statist Soc B 57 : 289 ~ 300
Banfi A / 2000 / Proliferation kinetics and differentiation potential of ex vivo expanded human bone marrow stromal cells: Implications for their use in cell therapy / Exp He
Baxter MA / 2004 / Study of telomere length reveals rapid aging of human marrow stromal cells following in vitro expansion / Stem Cells 22 : 675 ~ 682
Beausejour CM / 2003 / Reversal of human cellular senescence: roles of the p53 and p16 pathways / EMBO J 22 : 4212 ~ 4222
Benjamini Y / 1995 / Controlling the false discovery rate: a practical and powerful approach to multiple testing / J R Statist Soc B 57 : 289 ~ 300
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