DNA Hypermethylation in Somatic Cells Correlates with Higher Reprogramming Efficiency

被引:16
作者
Barrero, Maria J. [2 ]
Berdasco, Maria [1 ]
Paramonov, Ida [2 ]
Bilic, Josipa [2 ]
Vitaloni, Marianna [2 ]
Esteller, Manel [1 ,3 ]
Izpisua Belmonte, Juan Carlos [2 ,4 ]
机构
[1] Bellvitge Inst Biomed Res IDIBELL, Canc Epigenet Grp, Canc Epigenet & Biol Program PEBC, Barcelona 08908, Catalonia, Spain
[2] Ctr Regenerat Med Barcelona, Barcelona, Catalonia, Spain
[3] ICREA, Barcelona, Catalonia, Spain
[4] Salk Inst Biol Studies, La Jolla, CA 92037 USA
基金
欧洲研究理事会;
关键词
Reprogramming; Pluripotent stem cells; Gene expression; Induced pluripotent stem cells; Epigenetics; DNA methylation; PLURIPOTENT STEM-CELLS; HUMAN FIBROBLASTS; METHYLATION; GENERATION; INDUCTION; MOUSE; ES; MEMORY; MAPS;
D O I
10.1002/stem.1138
中图分类号
Q813 [细胞工程];
学科分类号
摘要
The efficiency of somatic cell reprogramming to pluripotency using defined factors is dramatically affected by the cell type of origin. Here, we show that human keratinocytes, which can be reprogrammed at a higher efficiency than fibroblast [Nat Biotechnol 2008;26:1276-1284], share more genes hypermethylated at CpGs with human embryonic stem cells (ESCs) than other somatic cells frequently used for reprogramming. Moreover, pluripotent cells reprogrammed from keratinocytes (KiPS) are more similar to ESCs than those reprogrammed from fibroblasts (FiPS) in regard to DNA methylation levels, mostly due to the presence of genes that fail to acquire high levels of DNA methylation in FiPS cells. We propose that higher reprogramming efficiency correlates with the hypermethylation of tissue-specific genes rather than with a more permissive pluripotency gene network. STEM CELLS 2012;30:1696-1702
引用
收藏
页码:1696 / 1702
页数:7
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