lithiumanantipsychoticdruggreatlyenhancesthegenerationofinducedpluripotentstemcells | |
Wang Quan1; Xu Xinxiu6; Li Jun3; Liu Jing4; Gu Haifeng1; Zhang Ru6; Chen Jiekai4; Kuang Yin5; Fei Jian5; Jiang Cong2 | |
刊名 | cellresearch
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2011 | |
卷号 | 21期号:10页码:1424 |
关键词 | MOUSE FIBROBLASTS SOMATIC-CELLS EXPRESSION COMPLEX NANOG OCT4 INHIBITOR PATHWAY LINES P53 lithium induced pluripotent stem cells iPS GSK3 beta Nanog LSD1 histone demethylase |
ISSN号 | 1001-0602 |
DOI | 10.1038/cr.2011.108 |
英文摘要 | Somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) by defined factors. The low efficiency of reprogramming and genomic integration of oncogenes and viral vectors limited the potential application of iPSCs. Here we report that Lithium (Li), a drug used to treat mood disorders, greatly enhances iPSC generation from both mouse embryonic fibroblast and human umbilical vein endothelial cells. Li facilitates iPSC generation with one (Oct4) or two factors (OS or OK). The effect of Li on promoting reprogramming only partially depends on its major target GSK3 beta. Unlike other GSK3 beta inhibitors, Li not only increases the expression of Nanog, but also enhances the transcriptional activity of Nanog. We also found that Li exerts its effect by promoting epigenetic modifications via downregulation of LSD1, a H3K4-specific histone demethylase. Knocking down LSD1 partially mimics Li's effect in enhancing reprogramming. Our results not only provide a straightforward method to improve the iPSC generation efficiency, but also identified a histone demethylase as a critical modulator for somatic cell reprogramming. |
资助项目 | [Chinese Academy of Sciences] ; [Ministry of Science and Technology of China] ; [National Natural Science Foundation of China] ; [Shanghai Commission of Science and Technology] |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.183/handle/2S10ELR8/287019] ![]() |
专题 | 中国科学院上海药物研究所 |
作者单位 | 1.中国科学院上海药物研究所 2.华东师范大学 3.Department of Chemistry, The Scripps Research Institute 4.中国科学院广州生物医药与健康研究院 5.Shanghai Research Center for Biomodel Organism 6.同济大学 |
推荐引用方式 GB/T 7714 | Wang Quan,Xu Xinxiu,Li Jun,et al. lithiumanantipsychoticdruggreatlyenhancesthegenerationofinducedpluripotentstemcells[J]. cellresearch,2011,21(10):1424. |
APA | Wang Quan.,Xu Xinxiu.,Li Jun.,Liu Jing.,Gu Haifeng.,...&Xie Xin.(2011).lithiumanantipsychoticdruggreatlyenhancesthegenerationofinducedpluripotentstemcells.cellresearch,21(10),1424. |
MLA | Wang Quan,et al."lithiumanantipsychoticdruggreatlyenhancesthegenerationofinducedpluripotentstemcells".cellresearch 21.10(2011):1424. |
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