Defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts.
Defining hypo-methylated regions of stem cell-specific promoters in human iPS cells derived from extra-embryonic amnions and lung fibroblasts.
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DOI：
10.1371/journal.pone.0013017
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发表时间：
2010-09-27
期刊：
影响因子：
3.7
通讯作者：
Umezawa A
中科院分区：
文献类型：
--
作者：
Nishino K;Toyoda M;Yamazaki-Inoue M;Makino H;Fukawatase Y;Chikazawa E;Takahashi Y;Miyagawa Y;Okita H;Kiyokawa N;Akutsu H;Umezawa A
人类诱导多能干（iPS）细胞目前被用作再生医学的强大资源。在非常早期的发育阶段，DNA甲基化在囊胚阶段下降到总体较低水平，胚胎干细胞就是从囊胚阶段衍生出来的。因此，与分化细胞相比，多能干细胞，如ES和iPS细胞，被认为具有低甲基化状态。然而，在源自胚胎外和胚胎细胞的 iPS 细胞中，“干性”的表观遗传机制仍然未知。我们使用 Illumina 的 Infinium HumanMmethylation27 检查了来自人类羊膜细胞和胎儿肺成纤维细胞的 6 种人类 iPS 细胞系以及两种人类 ES 细胞系和 8 种人类分化细胞系的全基因组 DNA 甲基化（覆盖 1,3862 个基因的 24,949 个 CpG 位点，大部分选自启动子区域）。相当一部分（807 个位点）在 iPS/ES 细胞和分化细胞之间表现出明显的甲基化水平差异，在 iPS/ES 细胞中观察到 87.6% 的高甲基化。然而，在编码转录因子的基因启动子中发现了有限部分具有低甲基化的 CpG 位点。因此，一组基因通过其启动子甲基化的减少而变得活跃。 SOX15、SALL4、TDGF1、PPP1R16B和SOX10以及POU5F1等23个基因被定义为SS-DMR（干细胞特异性差异甲基化区域）低甲基化且在iPS/ES细胞中高表达的基因。我们展示了人羊膜 iPS 细胞以及成纤维细胞 iPS 细胞的 DNA 甲基化谱，并定义了 SS-DMR。对源自不同细胞类型的 iPS 细胞的表观遗传信息的了解可以用作“干性”的特征，并且可以使我们能够筛选最佳的 iPS/ES 细胞，并验证和监测用于人类治疗应用的 iPS/ES 细胞衍生物。
Human induced pluripotent stem (iPS) cells are currently used as powerful resources in regenerative medicine. During very early developmental stages, DNA methylation decreases to an overall low level at the blastocyst stage, from which embryonic stem cells are derived.Therefore, pluripotent stem cells, such as ES and iPS cells, are considered to have hypo-methylated status compared to differentiated cells. However, epigenetic mechanisms of “stemness” remain unknown in iPS cells derived from extra-embryonic and embryonic cells. We examined genome-wide DNA methylation (24,949 CpG sites covering 1,3862 genes, mostly selected from promoter regions) with six human iPS cell lines derived from human amniotic cells and fetal lung fibroblasts as well as two human ES cell lines, and eight human differentiated cell lines using Illumina's Infinium HumanMethylation27. A considerable fraction (807 sites) exhibited a distinct difference in the methylation level between the iPS/ES cells and differentiated cells, with 87.6% hyper-methylation seen in iPS/ES cells. However, a limited fraction of CpG sites with hypo-methylation was found in promoters of genes encoding transcription factors. Thus, a group of genes becomes active through a decrease of methylation in their promoters. Twenty-three genes including SOX15, SALL4, TDGF1, PPP1R16B and SOX10 as well as POU5F1 were defined as genes with hypo-methylated SS-DMR (Stem cell-Specific Differentially Methylated Region) and highly expression in iPS/ES cells. We show that DNA methylation profile of human amniotic iPS cells as well as fibroblast iPS cells, and defined the SS-DMRs. Knowledge of epigenetic information across iPS cells derived from different cell types can be used as a signature for “stemness” and may allow us to screen for optimum iPS/ES cells and to validate and monitor iPS/ES cell derivatives for human therapeutic applications.
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影响因子：
14.9
作者：
Kanehisa M;Araki M;Goto S;Hattori M;Hirakawa M;Itoh M;Katayama T;Kawashima S;Okuda S;Tokimatsu T;Yamanishi Y
通讯作者：
Yamanishi Y
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
DOI：
10.1016/j.cub.2009.08.025
发表时间：
2009-11-03
期刊：
Current biology : CB
影响因子：
--
作者：
Maherali N;Hochedlinger K
通讯作者：
Hochedlinger K
影响因子：
46.9
作者：
Danwei Huangfu;Osafune, Kenji;Melton, Douglas A.
通讯作者：
Melton, Douglas A.