Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells.
Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells.
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DOI：
10.1038/nature09798
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发表时间：
2011-03-03
期刊：
影响因子：
64.8
通讯作者：
Ecker, Joseph R.
中科院分区：
文献类型：
--
作者：
Lister, Ryan;Pelizzola, Mattia;Kida, Yasuyuki S.;Hawkins, R. David;Nery, Joseph R.;Hon, Gary;Antosiewicz-Bourget, Jessica;O'Malley, Ronan;Castanon, Rosa;Klugman, Sarit;Downes, Michael;Yu, Ruth;Stewart, Ron;Ren, Bing;Thomson, James A.;Evans, Ronald M.;Ecker, Joseph R.
诱导多能干细胞（iPSC）为再生医学和疾病与发育研究提供了巨大的潜力。体细胞重编程涉及表观基因组重构，赋予iPSC与胚胎干细胞（ES细胞）相似的特征。然而，在整个基因组中，ES细胞样DNA甲基化模式的重建有多完整仍然是未知的。在这里，我们报告了第一个全基因组谱的DNA甲基化在单碱基分辨率在五个人类iPSC线，沿着甲基化的ES细胞，体细胞，分化的iPSC和ES细胞。iPSC显示出显著的重编程变异性，包括体细胞记忆和DNA甲基化的异常重编程。iPSC共享接近着丝粒和端粒的兆碱基规模差异甲基化区域，其显示非CG甲基化的不完全重编程，以及CG甲基化和组蛋白修饰的差异。最后，iPSC向滋养层细胞的分化揭示了重编程CG甲基化中的错误以高频率传递，提供了分化后维持的iPSC重编程特征。
Induced pluripotent stem cells (iPSCs) offer immense potential for regenerative medicine and studies of disease and development. Somatic cell reprogramming involves epigenomic reconfiguration, conferring iPSCs with characteristics similar to embryonic stem (ES) cells. However, it remains unknown how complete the reestablishment of ES-cell-like DNA methylation patterns is throughout the genome. Here we report the first whole-genome profiles of DNA methylation at single-base resolution in five human iPSC lines, along with methylomes of ES cells, somatic cells, and differentiated iPSCs and ES cells. iPSCs show significant reprogramming variability, including somatic memory and aberrant reprogramming of DNA methylation. iPSCs share megabase-scale differentially methylated regions proximal to centromeres and telomeres that display incomplete reprogramming of non-CG methylation, and differences in CG methylation and histone modifications. Lastly, differentiation of iPSCs into trophoblast cells revealed that errors in reprogramming CG methylation are transmitted at a high frequency, providing an iPSC reprogramming signature that is maintained after differentiation.
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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：
64.8
作者：
Park, In-Hyun;Zhao, Rui;Daley, George Q.
通讯作者：
Daley, George Q.
影响因子：
64.5
作者：
Soldner F;Hockemeyer D;Beard C;Gao Q;Bell GW;Cook EG;Hargus G;Blak A;Cooper O;Mitalipova M;Isacson O;Jaenisch R
通讯作者：
Jaenisch R
DOI：
10.1073/pnas.0910012107
发表时间：
2010-03-02
影响因子：
11.1
作者：
Hu, Bao-Yang;Weick, Jason P.;Zhang, Su-Chun
通讯作者：
Zhang, Su-Chun
影响因子：
64.5
作者：
Takahashi, Kazutoshi;Yamanaka, Shinya
通讯作者：
Yamanaka, Shinya