DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells.
DNA methylation pattern changes upon long-term culture and aging of human mesenchymal stromal cells.
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DOI：
10.1111/j.1474-9726.2009.00535.x
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发表时间：
2010-02
期刊：
影响因子：
7.8
通讯作者：
Wagner W
中科院分区：
文献类型：
--
作者：
Bork S;Pfister S;Witt H;Horn P;Korn B;Ho AD;Wagner W
在体外培养扩增的2-3个月内，间充质基质细胞（MSC）经历以细胞增大、分化潜能丧失和最终生长停滞为特征的复制性衰老。在这项研究中，我们分析了DNA甲基化的变化，长期培养的MSC使用HumanMethylation 27微阵列评估27 578独特的CpG位点。此外，我们比较了年轻和老年供体的MSC。总体而言，甲基化模式在长期培养和老化过程中保持不变，但在特定CpG位点观察到高度显著的差异。这些差异中的许多在同源异型盒基因和参与细胞分化的基因中被观察到。在亚硫酸氢盐转化后通过焦磷酸测序验证甲基化变化，并与基因表达数据进行比较。值得注意的是，MSC中的甲基化变化在长期培养和体内老化中重叠。这支持了复制性衰老和衰老代表由特定表观遗传修饰调控的发育过程的观点。
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.
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DOI：
10.1073/pnas.98.2.646
发表时间：
2001-01-16
影响因子：
11.1
作者：
O'Hare, MJ;Bond, J;Jat, PS
通讯作者：
Jat, PS
影响因子：
5.2
作者：
Marciniak-Czochra, Anna;Stiehl, Thomas;Wagner, Wolfgang
通讯作者：
Wagner, Wolfgang
影响因子：
64.8
作者：
Janzen, Viktor;Forkert, Randolf;Scadden, David T.
通讯作者：
Scadden, David T.
DOI：
10.1073/pnas.95.18.10614
发表时间：
1998-09-01
影响因子：
11.1
作者：
Cristofalo, VJ;Allen, RG;Beck, JC
通讯作者：
Beck, JC
影响因子：
5.2
作者：
Baxter, MA;Wynn, RF;Bellantuono, I
通讯作者：
Bellantuono, I