Defining differentially methylated regions specific for the acquisition of pluripotency and maintenance in human pluripotent stem cells via microarray.
Defining differentially methylated regions specific for the acquisition of pluripotency and maintenance in human pluripotent stem cells via microarray.
复制标题
通过微阵列定义人类多能干细胞多能性获得和维持特异的差异甲基化区域
DOI：
10.1371/journal.pone.0108350
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Fan Y
中科院分区：
文献类型：
--
作者：
He W;Kang X;Du H;Song B;Lu Z;Huang Y;Wang D;Sun X;Yu Y;Fan Y
背景表观遗传调控对于人类多能干细胞的维持至关重要。研究表明，多能干细胞，例如胚胎干细胞和诱导多能干细胞，与分化细胞相比似乎具有高甲基化状态。然而，维持干性并调节胚胎干细胞和诱导多能干细胞之间重编程的基因的表观遗传差异仍不清楚。此外，使用不同方法产生的诱导多能干细胞的差异甲基化模式需要进一步研究。方法在这里，我们使用 Illumina 的 Infinium HumanMmethylation450 BeadChip 测定了 10 种人类细胞系的 DNA 甲基化谱，包括 2 种 ESC 系、4 种病毒衍生的 iPSC 系、2 种附加体衍生的 iPSC 系以及 2 种 iPSC 来源的亲代细胞系。 iPSC 表现出与 ESC 类似的高甲基化状态，但与亲本细胞有明显差异。 iPSC 和 ESC 之间具有共同甲基化模式的基因被归类为干性的关键因素，而 iPSC 和 ESC 之间的差异表明 iPSC 部分保留了亲本特征，并在细胞重编程过程中获得了从头甲基化异常。病毒来源的 iPSC 和附加型来源的 iPSC 之间没有发现显着差异。这项研究详细确定了特定干细胞系的从头差异甲基化特征。结论 本研究描述了使用病毒和游离方法产生的人类 iPSC、相应的体细胞和 hESC 的 DNA 甲基化谱。 ss-DMR 和 ES-iPS-DMR 系列均具有高分辨率。对此类表观遗传信息的了解可以用作干性和自我更新的特征，并为选择用于人类再生医学的最佳多能干细胞提供潜在方法。
Background Epigenetic regulation is critical for the maintenance of human pluripotent stem cells. It has been shown that pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells, appear to have a hypermethylated status compared with differentiated cells. However, the epigenetic differences in genes that maintain stemness and regulate reprogramming between embryonic stem cells and induced pluripotent stem cells remain unclear. Additionally, differential methylation patterns of induced pluripotent stem cells generated using diverse methods require further study. Methodology Here, we determined the DNA methylation profiles of 10 human cell lines, including 2 ESC lines, 4 virally derived iPSC lines, 2 episomally derived iPSC lines, and the 2 parental cell lines from which the iPSCs were derived using Illumina's Infinium HumanMethylation450 BeadChip. The iPSCs exhibited a hypermethylation status similar to that of ESCs but with distinct differences from the parental cells. Genes with a common methylation pattern between iPSCs and ESCs were classified as critical factors for stemness, whereas differences between iPSCs and ESCs suggested that iPSCs partly retained the parental characteristics and gained de novo methylation aberrances during cellular reprogramming. No significant differences were identified between virally and episomally derived iPSCs. This study determined in detail the de novo differential methylation signatures of particular stem cell lines. Conclusions This study describes the DNA methylation profiles of human iPSCs generated using both viral and episomal methods, the corresponding somatic cells, and hESCs. Series of ss-DMRs and ES-iPS-DMRs were defined with high resolution. Knowledge of this type of epigenetic information could be used as a signature for stemness and self-renewal and provides a potential method for selecting optimal pluripotent stem cells for human regenerative medicine.
登录
查看更多内容
影响因子：
46.9
作者：
Deng, Jie;Shoemaker, Robert;Xie, Bin;Gore, Athurva;LeProust, Emily M.;Antosiewicz-Bourget, Jessica;Egli, Dieter;Maherali, Nimet;Park, In-Hyun;Yu, Junying;Daley, George Q.;Eggan, Kevin;Hochedlinger, Konrad;Thomson, James;Wang, Wei;Gao, Yuan;Zhang, Kun
通讯作者：
Zhang, Kun
影响因子：
23.9
作者：
Fouse, Shaun D.;Shen, Yin;Fan, Guoping
通讯作者：
Fan, Guoping
影响因子：
64.8
作者：
Park, In-Hyun;Zhao, Rui;Daley, George Q.
通讯作者：
Daley, George Q.
影响因子：
7
作者：
Bibikova, Marina;Chudin, Eugene;Fan, Jian-Bing
通讯作者：
Fan, Jian-Bing
影响因子：
12.3
作者：
Horvath S
通讯作者：
Horvath S