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Lithium, an anti-psychotic drug, greatly enhances the generation of induced pluripotent stem cells
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Lithium, an anti-psychotic drug, greatly enhances the generation of induced pluripotent stem cells
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Journal Article
Lithium, an anti-psychotic drug, greatly enhances the generation of induced pluripotent stem cells
2011
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Animals
/ Antipsychotic Agents - pharmacology
/ Biomedical and Life Sciences
/ Cell Dedifferentiation - drug effects
/ Drugs
/ Embryo, Mammalian - cytology
/ Embryo, Mammalian - metabolism
/ Endothelial Cells - cytology
/ Endothelial Cells - metabolism
/ genomics
/ Histone Demethylases - genetics
/ Histone Demethylases - metabolism
/ Histones
/ Homeodomain Proteins - genetics
/ Homeodomain Proteins - metabolism
/ Humans
/ Induced Pluripotent Stem Cells - cytology
/ Induced Pluripotent Stem Cells - metabolism
/ Inhibitory postsynaptic potentials
/ Lithium
/ Mice
/ Mood
/ Nanog
/ Original
/ Oxidoreductases, N-Demethylating - genetics
/ Oxidoreductases, N-Demethylating - metabolism
/ Umbilical Veins - metabolism
/ 人脐静脉内皮细胞
/ 多能干细胞
/ 精神病
/ 胚胎成纤维细胞
/ 药物
/ 诱导
/ 锂电池
