High-throughput sequencing reveals the disruption of methylation of imprinted gene in induced pluripotent stem cells

被引：42

作者：

Chang, Gang ^{[1
,2
]}

Gao, Shuai ^{[1
,2
]}

Hou, Xinfeng ^{[2
]}

Xu, Zijian ^{[2
]}

Liu, Yanfeng

Kang, Lan ^{[2
]}

Tao, Yu ^{[2
]}

Liu, Wenqiang ^{[2
]}

Huang, Bo ^{[2
]}

Kou, Xiaochen ^{[2
]}

Chen, Jiayu ^{[2
]}

An, Lei ^{[1
]}

Miao, Kai ^{[1
]}

Di, Keqian ^{[1
]}

Wang, Zhilong ^{[1
]}

Tan, Kun ^{[1
]}

Cheng, Tao

Cai, Tao ^{[2
]}

Gao, Shaorong ^{[2
]}

Tian, Jianhui ^{[1
]}

机构：

[1] China Agr Univ, Coll Anim Sci & Technol, Natl Engn Lab Anim Breeding, Key Lab Anim Genet Breeding & Reprod,Minist Agr, Beijing 100193, Peoples R China

[2] Natl Inst Biol Sci, Beijing, Peoples R China

来源：

CELL RESEARCH | 2014年 / 24卷 / 03期

基金：

中国国家自然科学基金;

关键词：

imprinted gene; somatic reprogramming; iPSCs; tetraploid complementation; DNA METHYLATION; TETRAPLOID COMPLEMENTATION; CHROMATIN-STRUCTURE; EPIGENETIC MEMORY; GROUND-STATE; HUMAN GENOME; MOUSE MURR1; IPS CELLS; CHIP-SEQ; RNA-SEQ;

D O I：

10.1038/cr.2013.173

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

It remains controversial whether the abnormal epigenetic modifications accumulated in the induced pluripotent stem cells (iPSCs) can ultimately affect iPSC pluripotency. To probe this question, iPSC lines with the same genetic background and proviral integration sites were established, and the pluripotency state of each iPSC line was characterized using tetraploid (4N) complementation assay. Subsequently, gene expression and global epigenetic modifications of "4N-ON" and the corresponding "4N-OFF" iPSC lines were compared through deep sequencing analyses of mRNA expression, small RNA profile, histone modifications (H3K27me3, H3K4me3, and H3K4me2), and DNA methylation. We found that methylation of an imprinted gene, Zrsr1, was consistently disrupted in the iPSC lines with reduced pluripotency. Furthermore, the disrupted methylation could not be rescued by improving culture conditions or subcloning of iPSCs. Moreover, the relationship between hypomethylation of Zrsr1 and pluripotency state of iPSCs was further validated in independent iPSC lines derived from other reprogramming systems.

引用

页码：293 / 306

页数：14

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