6月13日,Nature雜志在線報道了胚胎干細胞發(fā)育潛能性研究的重要進展,。(ES)來源于囊胚階段的胚胎,被認為功能上等同于內細胞團,。而內細胞團不能形成全部的胚胎外組織。
本研究發(fā)現(xiàn),,在小鼠ES和誘導多能干細胞(iPS)中有一群稀有而短暫存在的細胞高水平表達那些發(fā)現(xiàn)于2細胞期(2C)全能性囊胚的轉錄物。
研究者通過給2C樣ES細胞遺傳標記,發(fā)現(xiàn)它們缺乏內細胞團多能性蛋白Oct4 (也稱為Pou5f1), Sox2 和 Nanog,,并且具有發(fā)育為胚胎和胚胎外組織的能力,。
他們還在這種特殊的細胞狀態(tài)中發(fā)現(xiàn)了幾乎所有的ES細胞周期特點,。這些ES細胞周期是由組蛋白修飾酶控制的。轉錄組序列分析和生物信息分析顯示,,許多2C細胞轉錄物源自來源于內源逆轉錄病毒的長末端重復序列。這提示,,外源序列有助于驅動有胎盤哺乳動物的細胞命運調控。(生物谷bioon.com)
doi:10.1016/j.cell.2011.10.017
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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.