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首页> 外文期刊>Epigenetics & Chromatin >Differences in the epigenetic and reprogramming properties of pluripotent and extra-embryonic stem cells implicate chromatin remodelling as an important early event in the developing mouse embryo
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Differences in the epigenetic and reprogramming properties of pluripotent and extra-embryonic stem cells implicate chromatin remodelling as an important early event in the developing mouse embryo

机译：多能干和胚外干细胞表观遗传和重编程特性的差异表明染色质重塑是小鼠胚胎发育中的重要早期事件

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Background During early mouse development, two extra-embryonic lineages form alongside the future embryo: the trophectoderm (TE) and the primitive endoderm (PrE). Epigenetic changes known to take place during these early stages include changes in DNA methylation and modified histones, as well as dynamic changes in gene expression. Results In order to understand the role and extent of chromatin-based changes for lineage commitment within the embryo, we examined the epigenetic profiles of mouse embryonic stem (ES), trophectoderm stem (TS) and extra-embryonic endoderm (XEN) stem cell lines that were derived from the inner cell mass (ICM), TE and PrE, respectively. As an initial indicator of the chromatin state, we assessed the replication timing of a cohort of genes in each cell type, based on data that expressed genes and acetylated chromatin domains, generally, replicate early in S-phase, whereas some silent genes, hypoacetylated or condensed chromatin tend to replicate later. We found that many lineage-specific genes replicate early in ES, TS and XEN cells, which was consistent with a broadly 'accessible' chromatin that was reported previously for multiple ES cell lines. Close inspection of these profiles revealed differences between ES, TS and XEN cells that were consistent with their differing lineage affiliations and developmental potential. A comparative analysis of modified histones at the promoters of individual genes showed that in TS and ES cells many lineage-specific regulator genes are co-marked with modifications associated with active (H4ac, H3K4me2, H3K9ac) and repressive (H3K27me3) chromatin. However, in XEN cells several of these genes were marked solely by repressive modifications (such as H3K27me3, H4K20me3). Consistent with TS and XEN having a restricted developmental potential, we show that these cells selectively reprogramme somatic cells to induce the de novo expression of genes associated with extraembryonic differentiation. Conclusions These data provide evidence that the diversification of defined embryonic and extra-embryonic lineages is accompanied by chromatin remodelling at specific loci. Stem cell lines from the ICM, TE and PrE can each dominantly reprogramme somatic cells but reset gene expression differently, reflecting their separate lineage identities and increasingly restricted developmental potentials.
机译：背景技术在小鼠的早期发育过程中，与未来的胚胎一起形成了两个胚外谱系：滋养外胚层（TE）和原始内胚层（PrE）。已知在这些早期阶段发生的表观遗传学变化包括DNA甲基化和修饰的组蛋白变化，以及基因表达的动态变化。结果为了了解基于染色质的改变在胚胎中沿袭的作用和程度，我们检查了小鼠胚胎干（ES），滋养外胚层干（TS）和胚外内胚层（XEN）干细胞系的表观遗传概况它们分别来自内部细胞团（ICM），TE和PrE。作为染色质状态的初步指标，我们基于表达基因和乙酰化染色质结构域的数据通常在S期早期复制，而某些沉默基因被低乙酰化的情况下，评估了每种细胞类型中一组基因的复制时机。或浓缩的染色质倾向于稍后复制。我们发现，许多谱系特异性基因在ES，TS和XEN细胞中早期复制，这与先前报道的多种ES细胞系的广泛“可及”的染色质一致。仔细检查这些图谱可发现ES，TS和XEN细胞之间的差异，与它们不同的血统隶属关系和发育潜力一致。对单个基因启动子处修饰的组蛋白的比较分析表明，在TS和ES细胞中，许多谱系特异性调节基因与活性（H4ac，H3K4me2，H3K9ac）和阻抑（H3K27me3）染色质相关的修饰共同标记。但是，在XEN细胞中，这些基因中的几个仅通过抑制修饰来标记（例如H3K27me3，H4K20me3）。与具有有限的发展潜力的TS和XEN一致，我们表明这些细胞选择性地重编程体细胞，以诱导与胚外分化相关的基因的从头表达。结论这些数据提供了证据，即确定的胚胎和胚外谱系的多样化伴随着特定位点的染色质重塑。来自ICM，TE和PrE的干细胞系各自可以显着地重编程体细胞，但是以不同的方式重置基因表达，这反映了它们各自的谱系身份和日益受限的发展潜力。

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