Comparative FAIRE-seq analysis reveals distinguishing features of the chromatin structure of ground state- and primed-pluripotent cells.
Comparative FAIRE-seq analysis reveals distinguishing features of the chromatin structure of ground state- and primed-pluripotent cells.
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DOI：
10.1002/stem.1871
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发表时间：
2015-02
期刊：
影响因子：
5.2
通讯作者：
Dailey, Lisa
中科院分区：
文献类型：
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作者：
Murtha, Matthew;Strino, Francesco;Tokcaer-Keskin, Zeynep;Bayin, N. Sumru;Shalabi, Doaa;Xi, Xiangmei;Kluger, Yuval;Dailey, Lisa
多能胚胎干细胞(ESCs)和表皮干细胞(EpiSCs)均可在培养中自我更新或分化为初级生殖层，前者来源于植入前小鼠胚泡，后者来源于植入后胚胎。虽然核心转录因子OCT4、SOX2和NANOG在这两种细胞中都有表达，但基因表达谱和其他特征表明，ESCs和EpiSCs反映了体内不同发育成熟阶段的上胚细胞。因此，“幼稚的”或“基态的”ESCs类似于ICM的细胞，而“预置的”EpiSCs类似于移植后卵柱的细胞。为了深入了解幼稚和启动的多能细胞之间的关系，以及这些多能状态中的每一个与非多能细胞之间的关系，我们使用FIRE-SEQ生成了ESCs、EpiSCs、多潜能神经干细胞(NSCs)和小鼠胚胎成纤维细胞(MEF)中可访问的染色质区域的比较图谱。我们发现了多能细胞和体细胞的可及染色质模式之间的区别，这与ESCs和EpiSCs高度相关的表型一致。然而，通过定义开放染色质的细胞特异性和共享区，并将这些数据与已发表的基因表达和芯片分析相结合，我们还说明了幼稚和启动细胞染色质的独特特征。功能研究表明，多个阶段特异性增强子调控ESC或EpiSC特异性基因的表达，并暗示辅助TF是核心TF阶段特异性激活的重要调节器。总之，这些观察结果提供了对伴随着这些多能状态之间的转变的染色质结构动力学的洞察。
Both pluripotent Embryonic Stem Cells (ESCs), established from preimplantation murine blastocysts, and Epiblast Stem cells (EpiSCs), established from postimplantation embryos, can self-renew in culture or differentiate into each of the primary germ layers. While the core transcription factors (TFs) OCT4, SOX2, and NANOG are expressed in both cell types, the gene expression profiles and other features suggest that ESCs and EpiSCs reflect distinct developmental maturation stages of the epiblast in vivo. Accordingly, ‘naïve’ or ‘ground state’ ESCs resemble cells of the ICM, whereas ‘primed’ EpiSCs resemble cells of the postimplantation egg cylinder. To gain insight into the relationship between naïve and primed pluripotent cells, and of each of these pluripotent states to that of non-pluripotent cells, we have used FAIRE-seq to generate a comparative atlas of the accessible chromatin regions within ESCs, EpiSCs, multipotent Neural Stem cells (NSCs) and Mouse Embryonic Fibroblasts (MEFs). We find a distinction between the accessible chromatin patterns of pluripotent and somatic cells that is consistent with the highly related phenotype of ESCs and EpiSCs. However, by defining cell-specific- and shared regions of open chromatin, and integrating these data with published gene expression- and ChIP analyses, we also illustrate unique features of the chromatin of naïve- and primed cells. Functional studies suggest that multiple stage-specific enhancers regulate ESC- or EpiSC- specific gene expression, and implicate auxiliary TFs as important modulators for stage-specific activation by the core TFs. Together these observations provide insights into the chromatin structure dynamics accompanying transitions between these pluripotent states.
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影响因子：
64.8
作者：
Brons, I. Gabrielle M.;Smithers, Lucy E.;Vallier, Ludovic
通讯作者：
Vallier, Ludovic
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作者：
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