Signalling, cell cycle and pluripotency in embryonic stem cells.
Pluripotent mouse embryonic stem (ES) cells can be expanded in large numbers in vitro owing to a process of symmetrical self-renewal. Self-renewal entails proliferation with a concomitant suppression of differentiation. Here we describe how the cytokine leukaemia inhibitory factor (LIF) sustains self-renewal through activation of the transcription factor STAT3, and how two other signals - extracellular-signal-related kinase (ERK) and phosphatidylinositol-3-OH kinase (PI3K) - can influence differentiation and propagation, respectively. We relate these observations to the unusual cell-cycle properties of ES cells and speculate on the role of the cell cycle in maintaining pluripotency.
Burdon
Tom
T
Department of Gene Expression and Development, Roslin Institute, Midlothian, EH25 9PS, Roslin, UK.
Smith
Austin
A
Savatier
Pierre
P
D000818:Animals; D015703:Antigens, CD / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D016213:Cyclins / Q000378:metabolism; D050822:Cytokine Receptor gp130; D004268:DNA-Binding Proteins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D006131:Growth Inhibitors / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000502:physiology*; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism
D015703:Antigens, CD; D016213:Cyclins; D004268:DNA-Binding Proteins; D006131:Growth Inhibitors; C494199:IL6ST protein, human; C494200:Il6st protein, mouse; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D008562:Membrane Glycoproteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D050822:Cytokine Receptor gp130; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases