title: Melatonin-mediated upregulation of GLUT1 blocks exit from pluripotency by increasing the uptake of oxidized vitamin C in mouse embryonic stem cells.
abstract: Melatonin and vitamin C are powerful antioxidants that improve the reprogramming efficiency of induced pluripotent stem cells (iPSCs). However, the effects of the combined treatment of vitamin C and melatonin on the differentiation of embryonic stem cells (ESCs) have not yet been examined. In this study, we showed that melatonin synergizes with vitamin C to derail exit from pluripotency of mouse ESCs. This effect is related to the increased uptake of dehydroascorbate, the oxidized form of vitamin C, through glucose transporter 1 (Glut1) transporter, which in turn, is upregulated by melatonin treatment. Analysis of the cell signaling pathway profiling systems and specific pathway inhibition indicated that melatonin enhances Glut1 expression by activating the PI3K/AKT and MAPK/ERK signaling pathways. Our findings provide a theoretical basis for application of melatonin in research on ESCs and iPSCs and for further investigation of the effect of combinatorial compounds on cell reprogramming.-Wu, H., Song, C., Zhang, J., Zhao, J., Fu, B., Mao, T., Zhang, Y. Melatonin-mediated upregulation of GLUT1 blocks exit from pluripotency by increasing the uptake of oxidized vitamin C in mouse embryonic stem cells.
authors.affiliation: College of Veterinary Medicine, Northwest Agriculture and Forestry (A&F) University, Yangling, China; and hbwu029@nwsuaf.edu.cn.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Wu
authors.affiliation: College of Veterinary Medicine, Northwest Agriculture and Forestry (A&F) University, Yangling, China; and.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Song
authors.affiliation: College of Veterinary Medicine, Northwest Agriculture and Forestry (A&F) University, Yangling, China; and.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, China.
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Northwest Agriculture and Forestry (A&F) University, Yangling, China; and hbwu029@nwsuaf.edu.cn zhangy1956@sina.com.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, China.
authors.forename: Jiamin
authors.initials: J
authors.lastname: Zhao
authors.affiliation: College of Veterinary Medicine, Northwest Agriculture and Forestry (A&F) University, Yangling, China; and.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Fu
authors.affiliation: College of Veterinary Medicine, Northwest Agriculture and Forestry (A&F) University, Yangling, China; and.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, China.
authors.forename: Tingchao
authors.initials: T
authors.lastname: Mao
authors.affiliation: College of Veterinary Medicine, Northwest Agriculture and Forestry (A&F) University, Yangling, China; and zhangy1956@sina.com.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003683:Dehydroascorbic Acid / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D051272:Glucose Transporter Type 1; C495678:Slc2a1 protein, mouse; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D008550:Melatonin; D003683:Dehydroascorbic Acid
keywords: dehydroascorbic acid; differentiation; glucose transporter 1; signaling pathway