Molecular Criteria for Defining the Naive Human Pluripotent State - PubMed (nih.gov)

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摘要

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.
最近的研究旨在将培养的人类多能细胞转化为naive状态，但仍不清楚所得细胞在多大程度上概括了体内naive多能性。在这里，我们提出了一套分子标准，通过将其与人类胚胎进行比较来评估naive的人类多能状态。我们表明转座因子的转录提供了多能干细胞与早期人类发育之间一致性的敏感测量。我们还表明，naive状态的诱导伴随着全基因组 DNA 低甲基化，除印记基因外，这种低甲基化是可逆的，并且 X 染色体状态类似于人类植入前胚胎的状态。然而，我们没有看到naive人类细胞有效地掺入小鼠胚胎中。总体而言，我们测试的不同naive条件显示出基于分子标准与人类胚胎状态的不同关系，为未来分析naive人类多能性提供了背景。

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笔记