6月13日,Nature杂志在线报道了胚胎干细胞发育潜能性研究的重要进展。(ES)来源于囊胚阶段的胚胎,被认为功能上等同于内细胞团。而内细胞团不能形成全部的胚胎外组织。
本研究发现,在小鼠ES和诱导多能干细胞(iPS)中有一群稀有而短暂存在的细胞高水平表达那些发现于2细胞期(2C)全能性囊胚的转录物。
研究者通过给2C样ES细胞遗传标记,发现它们缺乏内细胞团多能性蛋白Oct4 (也称为Pou5f1), Sox2 和 Nanog,并且具有发育为胚胎和胚胎外组织的能力。
他们还在这种特殊的细胞状态中发现了几乎所有的ES细胞周期特点。这些ES细胞周期是由组蛋白修饰酶控制的。转录组序列分析和生物信息分析显示,许多2C细胞转录物源自来源于内源逆转录病毒的长末端重复序列。这提示,外源序列有助于驱动有胎盘哺乳动物的细胞命运调控。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
PMC:
PMID:
Embryonic stem cell potency fluctuateswith endogenous retrovirus activity
Todd S. Macfarlan,1, 4 Wesley D. Gifford,1 Shawn Driscoll,1 Karen Lettieri,1 Helen M. Rowe,2 Dario Bonanomi,1 Amy Firth,3 Oded Singer,3 Didier Trono2 & Samuel L. Pfaff1
Embryonic stem (ES) cells are derived from blastocyst-stage embryos and are thought to be functionally equivalent tothe inner cell mass, which lacks the ability to produce all extraembryonic tissues. Here we identify a rare transient cellpopulation within mouse ES and induced pluripotent stem (iPS) cell cultures that expresses high levels of transcriptsfound in two-cell (2C) embryos in which the blastomeres are totipotent. We genetically tagged these 2C-like ES cells andshow that they lack the inner cell mass pluripotency proteins Oct4 (also known as Pou5f1), Sox2 and Nanog, and haveacquired the ability to contribute to both embryonic and extraembryonic tissues. We show that nearly all ES cells cycle inand out of this privileged state, which is partially controlled by histone-modifying enzymes. Transcriptome sequencingand bioinformatic analyses showed that many 2C transcripts are initiated from long terminal repeats derived fromendogenous retroviruses, suggesting this foreign sequence has helped to drive cell-fate regulation in placentalmammals.