title: Foxm1 mediates LIF/Stat3-dependent self-renewal in mouse embryonic stem cells and is essential for the generation of induced pluripotent stem cells.
abstract: Activation of signal transducer and activator of transcription 3 (Stat3) by leukemia inhibitory factor (LIF) is required for maintaining self-renewal and pluripotency of mouse embryonic stem cells (mESCs). Here, we have confirmed transcription factor Forkhead Box m1 (Foxm1) as a LIF/Stat3 downstream target that mediates LIF/Stat3-dependent mESC self-renewal. The expression of Foxm1 relies on LIF signaling and is stimulated by Stat3 directly in mESCs. The knockdown of Foxm1 results in the loss of mESC pluripotency in the presence of LIF, and the overexpression of Foxm1 alone maintains mESC pluripotency in the absence of LIF and feeder layers, indicating that Foxm1 is a mediator of LIF/Stat3-dependent maintenance of pluripotency in mESCs. Furthermore, the inhibition of Foxm1 expression prevents the reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells (iPSCs), suggesting that Foxm1 is essential for the reprogramming of somatic cells into iPSCs. Our results reveal an essential function of Foxm1 in the LIF/Stat3-mediated mESC self-renewal and the generation of iPSCs.
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, Department of Biomedical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, Hunan, China.
authors.forename: Guixiang
authors.initials: G
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, Department of Biomedical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, Hunan, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, Department of Biomedical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, Hunan, China.
authors.forename: Tuanhui
authors.initials: T
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, Department of Biomedical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, Hunan, China.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Chemo/Biosensing and Chemometrics, Department of Biomedical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha, Hunan, China.
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Tan
mesh_terms: D000818:Animals; D054337:Cell Dedifferentiation; D053595:Embryonic Stem Cells / Q000166:cytology*; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D008297:Male; D051379:Mice; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D050796:STAT3 Transcription Factor
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