Embryonic stem cell potency fluctuates with endogenous retrovirus activity.
Embryonic stem cell potency fluctuates with endogenous retrovirus activity.
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DOI：
10.1038/nature11244
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发表时间：
2012-07-05
期刊：
影响因子：
64.8
通讯作者：
Pfaff, Samuel L.
中科院分区：
文献类型：
--
作者：
Macfarlan, Todd S.;Gifford, Wesley D.;Driscoll, Shawn;Lettieri, Karen;Rowe, Helen M.;Bonanomi, Dario;Firth, Amy;Singer, Oded;Trono, Didier;Pfaff, Samuel L.
胚胎干细胞(ES)来源于囊胚期胚胎，被认为在功能上等同于内细胞团，而内细胞团缺乏产生所有胚外组织的能力。在这里，我们报告了在小鼠胚胎干细胞和诱导多能干细胞(IPS)细胞培养中发现的罕见的瞬时细胞群体，这些细胞培养在两细胞(2C)胚胎中发现了高水平的转录本，在这些胚胎中，卵裂球是全能的。我们对这些2C样ES细胞进行了基因标记，发现它们缺乏ICM多能性蛋白Oct4、Sox2和Nanog，并获得了向胚胎和胚外组织贡献的能力。我们发现，几乎所有的ES细胞都进入和离开这种特权状态，我们发现这种特权状态部分受组蛋白修饰酶控制。转录组测序和生物信息学分析表明，相当数量的2C-转录本是由小鼠内源性逆转录病毒产生的长末端重复序列启动的，这表明这种外源序列有助于驱动胎盘哺乳动物的细胞命运调控。
Embryonic stem (ES) cells are derived from blastocyst stage embryos and are believed to be functionally equivalent to the inner cell mass, which lacks the ability to produce all extraembryonic tissues. Here we report the identification of a rare transient cell population within mouse ES and induced pluripotent stem (iPS) cell cultures that express high levels of transcripts found in two-cell (2C) embryos in which the blastomeres are totipotent. We genetically tagged these 2C-like ES cells and show that they lack the ICM pluripotency proteins Oct4, Sox2, and Nanog and have acquired the ability to contribute to both embryonic and extraembryonic tissues. We show that nearly all ES cells cycle in and out of this privileged state, which we find is partially controlled by histone modifying enzymes. Transcriptome sequencing and bioinformatic analyses revealed that a significant number of 2C-transcripts are initiated from long terminal repeats derived from murine endogenous retroviruses, suggesting this foreign sequence has helped to drive cell fate regulation in placental mammals.
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影响因子：
23.9
作者：
Hayashi K;de Sousa Lopes SMC;Tang F;Lao K;Surani MA
通讯作者：
Surani MA
影响因子：
30.8
作者：
Kunarso, Galih;Chia, Na-Yu;Bourque, Guillaume
通讯作者：
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影响因子：
3.6
作者：
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通讯作者：
Imai, H
DOI：
10.1073/pnas.0902925106
发表时间：
2009-07-21
影响因子：
11.1
作者：
Dupressoir, Anne;Vernochet, Cecile;Heidmann, Thierry
通讯作者：
Heidmann, Thierry
影响因子：
64.8
作者：
Chambers, Ian;Silva, Jose;Smith, Austin
通讯作者：
Smith, Austin