Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells.
Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells.
复制标题
非CG DNA甲基化是用于评估多能干细胞中内胚层分化能力的生物标志物。
DOI：
10.1038/ncomms10458
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发表时间：
2016-01-29
影响因子：
16.6
通讯作者：
Beck S
中科院分区：
文献类型：
--
作者：
Butcher LM;Ito M;Brimpari M;Morris TJ;Soares FAC;Ährlund-Richter L;Carey N;Vallier L;Ferguson-Smith AC;Beck S
非CG甲基化是多能干细胞的一个未知的表观遗传学特征。在这里，我们报告了非CG甲基化的减少与分化为内胚层的能力受损有关。对发现的25个表型人类诱导多能干细胞(HIPSC)系的2,670个非CG位点的全基因组分析显示，在25个(92%)HIPSC系中，23个(92%)的非CG甲基化单向丢失(Δβ=13%，P<；7.4×10−4)，正确识别内胚层分化能力。翻译成只有9个非CG位点的简化分析在发现队列中保持了预测能力(Δβ=23%，P<；9.1×10−6)，并正确地在由来自不同细胞类型和不同递送系统的hPSC以及人胚胎干细胞系组成的独立复制队列中识别了10个多能干细胞系中的9个内胚层分化能力。这一发现推断，当评估内胚层分化能力作为读数时，这些部位的非CG甲基化是一个生物标志物。非CpG残基的甲基化是多能细胞的一个鲜为人知的标志，随着细胞的分化逐渐丧失。在这里，作者指出非CG甲基化可以作为分化潜能的标志。
Non-CG methylation is an unexplored epigenetic hallmark of pluripotent stem cells. Here we report that a reduction in non-CG methylation is associated with impaired differentiation capacity into endodermal lineages. Genome-wide analysis of 2,670 non-CG sites in a discovery cohort of 25 phenotyped human induced pluripotent stem cell (hiPSC) lines revealed unidirectional loss (Δβ=13%, P<7.4 × 10−4) of non-CG methylation that correctly identifies endodermal differentiation capacity in 23 out of 25 (92%) hiPSC lines. Translation into a simplified assay of only nine non-CG sites maintains predictive power in the discovery cohort (Δβ=23%, P<9.1 × 10−6) and correctly identifies endodermal differentiation capacity in nine out of ten pluripotent stem cell lines in an independent replication cohort consisting of hiPSCs reprogrammed from different cell types and different delivery systems, as well as human embryonic stem cell (hESC) lines. This finding infers non-CG methylation at these sites as a biomarker when assessing endodermal differentiation capacity as a readout. The methylation of non-CpG residues is a poorly understood marker of pluripotent cells, gradually lost as cells differentiate. Here the authors show non-CG methylation can be used as a marker of differentiation potential.