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Genome-scale DNA Methylation analysis in distinct pluripotent stem cells.

机译：在不同的多能干细胞中进行基因组规模的DNA甲基化分析。

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摘要

Mouse embryonic stem cells (ESCs) and embryonic germ cells (EGCs) are both pluripotent cell types derived from distinct developmental stages. Despite sharing many characteristics, some differences have been reported between the two cell types. For instance, EGCs generally lack of DNA methylation at imprinted regions and they have been suggested to display overall global hypomethylation. These characteristics have always been regarded as reflective of their derivation origin from primordial germ cells (PGCs), whereas ESCs are derived from preimplantation blastocysts. A large set of newly derived, genetically matched ESC and EGC lines has enabled us to clarify several of these observations at genome-wide scale. DNA methylation analysis of ESCs and EGCs, in particular lines derived from both sexes demonstrates that the DNA methylation profiles of female ESCs and EGCs are comparable low, while the male cell lines all share a more hypermethylated genome. The observed hypomethylation is not restricted to promoters but is also evident in many retroelements including the regions often regarded as resistant to demethylation. Mechanistically it appears that the two active X chromosomes in female cells are involved. Specifically, we find that the X-linked gene Dusp9 may play a central role in the regulation of DNA methylation via the inhibition of Erk signaling. Taken together, our results provide novel mechanistic insights as well as clarify that it is not the EGC identity that caused the global hypomethylation in prior studies, but rather the fact that the lines in those experiments happened to be female EGCs.
机译：小鼠胚胎干细胞（ESC）和胚胎生殖细胞（EGC）都是来自不同发育阶段的多能细胞类型。尽管具有许多特征，但已报道了两种细胞类型之间的某些差异。例如，EGC通常在印迹区域缺乏DNA甲基化，并且已经建议它们显示总体的全局甲基化不足。这些特征一直被认为是它们源自原始生殖细胞（PGC）的来源，而ESC则来自植入前的胚泡。大量新近获得的，遗传匹配的ESC和EGC品系使我们能够在全基因组范围内阐明其中一些观察结果。 ESC和EGC的DNA甲基化分析，特别是从两性衍生的品系表明，雌性ESC和EGC的DNA甲基化谱图相当低，而雄性细胞系均共享更高甲基化的基因组。观察到的低甲基化不仅限于启动子，而且在许多逆转录元件中也很明显，包括通常被认为对脱甲基有抗性的区域。从机理上讲，似乎涉及女性细胞中的两个活跃的X染色体。具体来说，我们发现X连锁基因Dusp9可能通过抑制Erk信号在DNA甲基化的调节中发挥核心作用。综上所述，我们的结果提供了新颖的机械学见解，并阐明了导致先前的研究中整体甲基化不足的不是EGC身份，而是这些实验中的血统恰好是女性EGC的事实。

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  • 作者

    Webster, Jamie Orme.;

  • 作者单位

    Harvard University.;

  • 授予单位 Harvard University.;
  • 学科 Biology Genetics.;Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 2014
  • 页码 96 p.
  • 总页数 96
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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