Volume 21, No 10, Oct 2011

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 21 Issue 10, October 2011: 1424-1435

ORIGINAL ARTICLES

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

Quan Wang¹, Xinxiu Xu², Jun Li³, Jing Liu⁴, Haifeng Gu¹, Ru Zhang², Jiekai Chen⁴, Yin Kuang⁵, Jian Fei⁵, Cong Jiang⁶, Ping Wang⁶,

¹State Key Laboratory of Drug Research, the National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China

²Shanghai Key Laboratory of Signaling and Disease Research, Laboratory of Receptor-based Bio-medicine, School of Life Sciences and Technology, Tongji University, Shanghai, China

³Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

⁴Key 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

⁵Shanghai Research Center for Biomodel Organism, Shanghai, China

⁶Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China Correspondence: Xin Xie,(xxie@mail.shcnc.ac.cn)

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�. Unlike other GSK3� 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.

Cell Research (2011) 21:1424-1435. doi:10.1038/cr.2011.108; published online 5 July 2011

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