title: Glutathione peroxidase-1 is required for self-renewal of murine embryonic stem cells.
abstract: Embryonic stem (ES) cells are pluripotent cells that are capable of giving rise to any type of cells in the body and possess unlimited self-renewal potential. However, the exact regulatory mechanisms that govern the self-renewal ability of ES cells remain elusive. To understand the immediate early events during ES cell differentiation, we performed a proteomics study and analyzed the proteomic difference in murine ES cells before and after a 6-h spontaneous differentiation. We found that the expression level of glutathione peroxidase-1 (GPx-1), an antioxidant enzyme, is dramatically decreased upon the differentiation. Both knockdown of GPx-1 expression with shRNA and inhibiting GPx-1 activity by inhibitor led to the differentiation of ES cells. Furthermore, we showed that during early differentiation, the quick degradation of GPx-1 was mediated by proteasome. Thus, our data indicated that GPx-1 is a key regulator of self-renewal of murine embryonic stem cells.
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Rd., Beijing 100850, China.
authors.forename: Qian-Yi
authors.initials: QY
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Rd., Beijing 100850, China.
authors.forename: Zhao-Shan
authors.initials: ZS
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Rd., Beijing 100850, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Rd., Beijing 100850, China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Rd., Beijing 100850, China.
authors.forename: Ang
authors.initials: A
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Rd., Beijing 100850, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Rd., Beijing 100850, China.
authors.forename: Xin-Zheng
authors.initials: XZ
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Rd., Beijing 100850, China.
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Rd., Beijing 100850, China.
authors.forename: Qiu-Ying
authors.initials: QY
authors.lastname: Han
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Rd., Beijing 100850, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Rd., Beijing 100850, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Rd., Beijing 100850, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Song
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Rd., Beijing 100850, China.
authors.forename: Wei-Hua
authors.initials: WH
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Rd., Beijing 100850, China. Electronic address: tli@ncba.ac.cn.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D005979:Glutathione Peroxidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007976:Leupeptins / Q000494:pharmacology; D051379:Mice; D039904:Pluripotent Stem Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D013870:Thiomalates / Q000494:pharmacology; D000094765:Glutathione Peroxidase GPX1
chemical_list: D004791:Enzyme Inhibitors; D007976:Leupeptins; D061988:Proteasome Inhibitors; D034741:RNA, Small Interfering; D013870:Thiomalates; C046062:2-thiomalic acid; D005979:Glutathione Peroxidase; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse
keywords: Differentiation; Embryonic stem cells; Glutathione peroxidase-1; Self-renewal