Deciphering the heterogeneity in DNA methylation patterns during stem cell differentiation and reprogramming.
Deciphering the heterogeneity in DNA methylation patterns during stem cell differentiation and reprogramming.
复制标题
破译干细胞分化和重编程过程中 DNA 甲基化模式的异质性
DOI：
10.1186/1471-2164-15-978
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发表时间：
2014-11-18
期刊：
影响因子：
4.4
通讯作者：
Xie H
中科院分区：
文献类型：
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作者：
Shao X;Zhang C;Sun MA;Lu X;Xie H
背景人类诱导多能干细胞（induced pluripotent stem cells，iPSCs）在基础研究、疾病建模和药物筛选等领域有着广泛的应用。具有异常DNA甲基化的表观遗传不稳定的iPSC可以分裂和分化成癌细胞。不幸的是，很少有人将iPSC的表观遗传变异与分化细胞的表观遗传变异进行比较。在这里，我们开发了一种分析方法来破译混合细胞的DNA甲基化异质性，并进一步利用它来定量评估脂肪源性干细胞（ADS）甲基化组中的DNA甲基化变异，从ADS细胞分化的成熟脂肪细胞（ADS-脂肪）和从ADS细胞重编程的iPSC（ADS-iPSCs）结果我们观察到不同基因组区域的DNA甲基化变异程度不同，启动子和5 'UTR区域表现出低甲基化变异，卫星区域表现出高甲基化变异。甲基化变异。与分化的细胞相比，ADS-iPSCs具有整体减少的甲基化变异，特别是在重复元件中。有趣的是，DNA甲基化变异在分化过程中在启动子区域减少，但在重编程过程中增加。启动子区的甲基化变异与基因表达呈负相关。此外，显示双极甲基化模式的基因，完全甲基化和完全未甲基化的读数，与碳水化合物代谢过程，细胞发育，细胞生长，增殖等。ConclusionsThis研究提供了一种方法来检测细胞亚群特异性甲基化基因在混合细胞群，并提供了一个更好的理解在干细胞分化和重编程的甲基化动力学。
BackgroundHuman induced pluripotent stem cells (iPSCs) have a wide range of applications throughout the fields of basic research, disease modeling and drug screening. Epigenetic instable iPSCs with aberrant DNA methylation may divide and differentiate into cancer cells. Unfortunately, little effort has been taken to compare the epigenetic variation in iPSCs with that in differentiated cells. Here, we developed an analytical procedure to decipher the DNA methylation heterogeneity of mixed cells and further exploited it to quantitatively assess the DNA methylation variation in the methylomes of adipose-derived stem cells (ADS), mature adipocytes differentiated from ADS cells (ADS-adipose) and iPSCs reprogrammed from ADS cells (ADS-iPSCs).ResultsWe observed that the degree of DNA methylation variation varies across distinct genomic regions with promoter and 5’UTR regions exhibiting low methylation variation and Satellite showing high methylation variation. Compared with differentiated cells, ADS-iPSCs possess globally decreased methylation variation, in particular in repetitive elements. Interestingly, DNA methylation variation decreases in promoter regions during differentiation but increases during reprogramming. Methylation variation in promoter regions is negatively correlated with gene expression. In addition, genes showing a bipolar methylation pattern, with both completely methylated and completely unmethylated reads, are related to the carbohydrate metabolic process, cellular development, cellular growth, proliferation, etc.ConclusionsThis study delivers a way to detect cell-subset specific methylation genes in a mixed cell population and provides a better understanding of methylation dynamics during stem cell differentiation and reprogramming.
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影响因子：
3.9
作者：
Ooi SK;Wolf D;Hartung O;Agarwal S;Daley GQ;Goff SP;Bestor TH
通讯作者：
Bestor TH
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Sugii, Shigeki;Kida, Yasuyuki;Berggren, W. Travis;Evans, Ronald M.
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Evans, Ronald M.
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通讯作者：
Kent WJ
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64.8
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