Lithium, an anti-psychotic drug, greatly enhances the generation of induced pluripotent stem cells  

作　　者：Quan Wang Xinxiu Xu Jun Li Jing Liu Haifeng Gu Ru Zhang Jiekai Chen Yin Kuang Jian Fei Cong Jiang Ping Wang Duanqing Pei Sheng Ding Xin Xie 

机构地区：[1]State Key Laboratory of Drug Research, the National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China [2]Shanghai Key Laboratory of Signaling and Diseas＇e Research, Laboratory of Receptor-based Bio-medicine, School of Life Sciences and Technology, Tongji University. Shanghai, China [3]Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA [4]Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China [5]Shanghai Research Center for Biomodel Organism, Shanghai, China [6]Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai China

出　　处：《Cell Research》2011年第10期1424-1435,共12页细胞研究（英文版）

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 GSK3β Unlike other GSK3β 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.

关 键 词：LITHIUM induced pluripotent stem cells IPS GSK3Β NANOG LSDI histone demethylase 

分 类 号：Q813[生物学—生物工程] TM911.14[电气工程—电力电子与电力传动]