Epigenetic signatures associated with different levels of differentiation potential in human stem cells.
Epigenetic signatures associated with different levels of differentiation potential in human stem cells.
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DOI：
10.1371/journal.pone.0007809
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发表时间：
2009-11-13
期刊：
影响因子：
3.7
通讯作者：
Prosper F
中科院分区：
文献类型：
--
作者：
Aranda P;Agirre X;Ballestar E;Andreu EJ;Román-Gómez J;Prieto I;Martín-Subero JI;Cigudosa JC;Siebert R;Esteller M;Prosper F
多能干细胞的治疗用途取决于它们的分化潜力，这已被证明是不同人群的变量。这些差异很可能是它们的表观遗传谱发生关键变化的结果。为了解决这个问题，我们研究了多能胚胎干细胞（ESC）和多能成体干细胞（ASC）在转录组、甲基组、组蛋白修饰和microRNA水平上的表观遗传调控水平。基因表达谱的差异允许将干细胞分为三个不同的群体，包括ESC、多能成体祖细胞（MAPC）和间充质基质细胞（MSC）。分化和多能基因的PcG抑制标记、组蛋白修饰和基因启动子甲基化分析表明，具有更广泛分化潜力的干细胞群体（ESC和MAPC）在分化基因中表现出更强的表观遗传抑制标记，并且这种表观遗传标记随着干细胞潜力的限制而逐渐消失。我们对microRNA的分析建立了特异性的microRNA特征，表明特异性的microRNA参与了多能性和分化基因的调控。我们的研究使我们提出了一个模型，其中表观遗传调控水平，作为DNA甲基化和组蛋白修饰标记的组合，在分化基因上定义了从祖细胞和多能干细胞到多能干细胞的分化潜力程度。
The therapeutic use of multipotent stem cells depends on their differentiation potential, which has been shown to be variable for different populations. These differences are likely to be the result of key changes in their epigenetic profiles. to address this issue, we have investigated the levels of epigenetic regulation in well characterized populations of pluripotent embryonic stem cells (ESC) and multipotent adult stem cells (ASC) at the trancriptome, methylome, histone modification and microRNA levels. Differences in gene expression profiles allowed classification of stem cells into three separate populations including ESC, multipotent adult progenitor cells (MAPC) and mesenchymal stromal cells (MSC). The analysis of the PcG repressive marks, histone modifications and gene promoter methylation of differentiation and pluripotency genes demonstrated that stem cell populations with a wider differentiation potential (ESC and MAPC) showed stronger representation of epigenetic repressive marks in differentiation genes and that this epigenetic signature was progressively lost with restriction of stem cell potential. Our analysis of microRNA established specific microRNA signatures suggesting specific microRNAs involved in regulation of pluripotent and differentiation genes. Our study leads us to propose a model where the level of epigenetic regulation, as a combination of DNA methylation and histone modification marks, at differentiation genes defines degrees of differentiation potential from progenitor and multipotent stem cells to pluripotent stem cells.
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