Changing nuclear landscape and unique PML structures during early epigenetic transitions of human embryonic stem cells.
Changing nuclear landscape and unique PML structures during early epigenetic transitions of human embryonic stem cells.
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DOI：
10.1002/jcb.22183
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发表时间：
2009-07-01
影响因子：
4
通讯作者：
Lawrence, Jeanne B.
中科院分区：
文献类型：
--
作者：
Butler, John T.;Hall, Lisa L.;Smith, Kelly P.;Lawrence, Jeanne B.
关键词：
体细胞复杂的核结构对表观基因组调控很重要，但人类胚胎干细胞（hESC）的核组织情况却鲜为人知。在此我们研究了多能性及处于转变过程中的人类胚胎干细胞的几种核结构。对着丝粒、端粒、SC35斑点、卡哈尔体、核纤层蛋白A/C和伊默菌素、核的形状和大小的观察表明，人类胚胎干细胞具有非常不同的“核景观”。这种景观在一个短暂的转变阶段发生重塑，与分化开始同时或就在分化开始之前。值得注意的是，人类胚胎干细胞最初含有大量剪接体组装因子SC35的信号，但缺乏离散的SC35结构域；这些结构域在细胞开始特化时形成，可能反映了细胞类型特异性的基因组组织。与此同时，随着核纤层蛋白A/C和伊默菌素整合到核纤层中，核的大小增加且形状改变。在这个短暂的阶段，人类胚胎干细胞呈现出截然不同的由早幼粒细胞白血病蛋白（PML）界定的结构，在体细胞中这些结构与基因调控和癌症相关。与体细胞中众多球形的早幼粒细胞白血病蛋白体不同，人类胚胎干细胞常常呈现出约1 - 3个两种形态类型的大型早幼粒细胞白血病蛋白结构：长线性“杆状”或复杂的“玫瑰花结状”，它们缺乏大量的小泛素样修饰蛋白1（SUMO - 1）、Daxx和Sp100。这些结构主要在分化的第0 - 2天出现，之后变得罕见。早幼粒细胞白血病蛋白杆状结构可能在其他结构（如着丝粒）之间“拉紧”，但明显与核纤层有某种关联，在早期核纤层蛋白A/C染色中，早幼粒细胞白血病蛋白常常邻接或填充一个“缺口”。研究结果表明，多能性人类胚胎干细胞具有明显不同的整体核结构，其重塑与早期表观基因组编程相关，并涉及独特的由早幼粒细胞白血病蛋白界定的结构的形成。
The complex nuclear structure of somatic cells is important to epigenomic regulation, yet little is known about nuclear organization of human embryonic stem cells (hESC). Here we surveyed several nuclear structures in pluripotent and transitioning hESC. Observations of centromeres, telomeres, SC35 speckles, Cajal Bodies, lamin A/C and emerin, nuclear shape and size demonstrate a very different “nuclear landscape” in hESC. This landscape is remodeled during a brief transitional window, concomitant with or just prior to differentiation onset. Notably, hESC initially contain abundant signal for spliceosome assembly factor, SC35, but lack discrete SC35 domains; these form as cells begin to specialize, likely reflecting cell-type specific genomic organization. Concomitantly, nuclear size increases and shape changes as lamin A/C and emerin incorporate into the lamina. During this brief window, hESC exhibit dramatically different PML-defined structures, which in somatic cells are linked to gene regulation and cancer. Unlike the numerous, spherical somatic PML bodies, hES cells often display ~1–3 large PML structures of two morphological types: long linear “rods” or elaborate “rosettes”, which lack substantial SUMO-1, Daxx, and Sp100.These occur primarily between Day 0–2 of differentiation and become rare thereafter. PML rods may be “taut” between other structures, such as centromeres, but clearly show some relationship with the lamina, where PML often abuts or fills a “gap” in early lamin A/C staining. Findings demonstrate that pluripotent hES cells have a markedly different overall nuclear architecture, remodeling of which is linked to early epigenomic programming and involves formation of unique PML-defined structures.
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DOI：
10.1083/jcb.152.5.1099
发表时间：
2001-03-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Boisvert FM;Kruhlak MJ;Box AK;Hendzel MJ;Bazett-Jones DP
通讯作者：
Bazett-Jones DP
临时细胞性白血病核体的行为是DNA损伤传感器，其对DNA双链断裂的反应由NBS1和激酶ATM，CHK2和ATR调节。
DOI：
10.1083/jcb.200604009
发表时间：
2006-10-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Dellaire G;Ching RW;Ahmed K;Jalali F;Tse KC;Bristow RG;Bazett-Jones DP
通讯作者：
Bazett-Jones DP
DOI：
10.1083/jcb.112.5.785
发表时间：
1991-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ascoli CA;Maul GG
通讯作者：
Maul GG
影响因子：
9.2
作者：
Brandt, A;Papagiannouli, F;Grosshans, J
通讯作者：
Grosshans, J
影响因子：
6.6
作者：
Olins, Ada L.;Zwerger, Monika;Olins, Donald E.
通讯作者：
Olins, Donald E.