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

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.
最近的研究旨在將培養(yǎng)的人類(lèi)多能細(xì)胞轉(zhuǎn)化為naive狀態(tài)，但仍不清楚所得細(xì)胞在多大程度上概括了體內(nèi)naive多能性。在這里，我們提出了一套分子標(biāo)準(zhǔn)，通過(guò)將其與人類(lèi)胚胎進(jìn)行比較來(lái)評(píng)估naive的人類(lèi)多能狀態(tài)。我們表明轉(zhuǎn)座因子的轉(zhuǎn)錄提供了多能干細(xì)胞與早期人類(lèi)發(fā)育之間一致性的敏感測(cè)量。我們還表明，naive狀態(tài)的誘導(dǎo)伴隨著全基因組 DNA 低甲基化，除印記基因外，這種低甲基化是可逆的，并且 X 染色體狀態(tài)類(lèi)似于人類(lèi)植入前胚胎的狀態(tài)。然而，我們沒(méi)有看到naive人類(lèi)細(xì)胞有效地?fù)饺胄∈笈咛ブ小？傮w而言，我們測(cè)試的不同naive條件顯示出基于分子標(biāo)準(zhǔn)與人類(lèi)胚胎狀態(tài)的不同關(guān)系，為未來(lái)分析naive人類(lèi)多能性提供了背景。

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