Hotspots of aberrant epigenomic reprogramming in human induced pluripotent stem cells

被引：1098

作者：

Lister, Ryan ^{[1
]}

Pelizzola, Mattia ^{[1
]}

Kida, Yasuyuki S. ^{[2
]}

Hawkins, R. David ^{[3
]}

Nery, Joseph R. ^{[1
]}

Hon, Gary ^{[3
]}

Antosiewicz-Bourget, Jessica ^{[4
,5
]}

O'Malley, Ronan ^{[1
]}

Castanon, Rosa ^{[1
]}

Klugman, Sarit ^{[3
]}

Downes, Michael ^{[2
]}

Yu, Ruth ^{[2
]}

Stewart, Ron ^{[4
,5
]}

Ren, Bing ^{[3
,6
]}

Thomson, James A. ^{[4
,5
,7
,8
]}

Evans, Ronald M. ^{[2
]}

Ecker, Joseph R. ^{[1
]}

机构：

[1] Salk Inst Biol Studies, Genome Anal Lab, La Jolla, CA 92037 USA

[2] Salk Inst Biol Studies, Howard Hughes Med Inst, Gene Express Lab, La Jolla, CA 92037 USA

[3] Ludwig Inst Canc Res, La Jolla, CA 92093 USA

[4] Morgridge Inst Res, Madison, WI 53707 USA

[5] Genome Ctr Wisconsin, Madison, WI 53706 USA

[6] Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA

[7] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53715 USA

[8] Univ Wisconsin, Dept Anat, Madison, WI 53706 USA

来源：

NATURE | 2011年 / 471卷 / 7336期

基金：

美国国家科学基金会; 美国国家卫生研究院; 日本学术振兴会;

关键词：

DNA METHYLATION; DIFFERENTIATION; GENES; MICE;

D O I：

10.1038/nature09798

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：68 / U84

页数：8