Molecular Criteria for Defining the Naive Human Pluripotent State.
Molecular Criteria for Defining the Naive Human Pluripotent State.
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DOI：
10.1016/j.stem.2016.06.011
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发表时间：
2016-10-06
期刊：
影响因子：
23.9
通讯作者：
Jaenisch, Rudolf
中科院分区：
文献类型：
--
作者：
Theunissen, Thorold W.;Friedli, Marc;He, Yupeng;Planet, Evarist;O'Neil, Ryan C.;Markoulaki, Styliani;Pontis, Julien;Wang, Haoyi;Iouranova, Alexandra;Imbeault, Michael;Duc, Julien;Cohen, Malkiel A.;Wert, Katherine J.;Castanon, Rosa;Zhang, Zhuzhu;Huang, Yanmei;Nery, Joseph R.;Drotar, Jesse;Lungjangwa, Tenzin;Trono, Didier;Ecker, Joseph R.;Jaenisch, Rudolf
最近的研究旨在将培养的人类多潜能细胞转变为幼稚状态，但目前尚不清楚由此产生的细胞在体内幼稚多能性中概括到什么程度。在这里，我们提出了一套通过将其与人类胚胎进行比较来评估人类原始多能性状态的分子标准。我们发现，转座元件的转录为多能干细胞和早期人类发育之间的一致性提供了一种灵敏的衡量标准。我们还表明，诱导幼稚状态伴随着全基因组DNA的低甲基化，这种低甲基化是可逆的，除了印记基因，并且X染色体的状态类似于人类植入前胚胎。然而，我们没有看到幼稚的人类细胞有效地整合到小鼠胚胎中。总体而言，根据分子标准，我们测试的不同幼稚条件显示出与人类胚胎状态的不同关系，为未来分析幼稚人类的多能性提供了背景。幼稚的人ESCs与卵裂期的胚胎具有独特的转座子特征。幼稚的人ESCs的全球DNA去甲基化是可逆的，除了印迹位点。幼稚的人ESCs的X染色体状态类似于植入前的胚胎，幼稚的人ESCs非常低效地整合到小鼠桑椹胚或囊胚中。使用基于转座子表达、DNA甲基化和X染色体状态的分子标准来比较原始的人类多能细胞和人类植入前胚胎。目前的方法产生的细胞最接近于桑拿期/早期囊胚期。
Recent studies have aimed to convert cultured human pluripotent cells to a naive state, but it remains unclear to what extent the resulting cells recapitulate in vivo naive pluripotency. Here we propose a set of molecular criteria for evaluating the naive human pluripotent state by comparing it to the human embryo. We show that transcription of transposable elements provides a sensitive measure of the concordance between pluripotent stem cells and early human development. We also show that induction of the naive state is accompanied by genome-wide DNA hypomethylation, which is reversible except at imprinted genes, and that the X chromosome status resembles that of the human preimplantation embryo. However, we did not see efficient incorporation of naive human cells into mouse embryos. Overall, the different naive conditions we tested showed varied relationships to human embryonic states based on molecular criteria, providing a backdrop for future analysis of naive human pluripotency. Naive human ESCs share a unique transposon signature with cleavage-stage embryos Global DNA demethylation in naive human ESCs is reversible except at imprinted loci The X chromosome status of naive human ESCs resembles the preimplantation embryo Naive human ESCs incorporate into the mouse morula or blastocyst very inefficiently Theunissen et al. use molecular criteria based on transposon expression, DNA methylation, and X chromosome status to compare naive human pluripotent cells to human preimplantation embryos. Current approaches yield cells that most closely resemble the morula/early blastocyst stage.
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