Signalling, cell cycle and pluripotency in embryonic stem cells

Trends Cell Biol. 2002 Sep;12(9):432-8. doi: 10.1016/s0962-8924(02)02352-8.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, CD / physiology
  • Cell Cycle / physiology*
  • Cell Differentiation / physiology
  • Cell Division / physiology
  • Cyclins / metabolism
  • Cytokine Receptor gp130
  • DNA-Binding Proteins / metabolism
  • Embryo, Mammalian / cytology
  • Growth Inhibitors / metabolism
  • Humans
  • Interleukin-6*
  • Leukemia Inhibitory Factor
  • Lymphokines / metabolism
  • Membrane Glycoproteins / physiology
  • Mice
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Biological
  • Phosphatidylinositol 3-Kinases / metabolism
  • Pluripotent Stem Cells / physiology*
  • STAT3 Transcription Factor
  • Signal Transduction / physiology*
  • Trans-Activators / metabolism

Substances

  • Antigens, CD
  • Cyclins
  • DNA-Binding Proteins
  • Growth Inhibitors
  • IL6ST protein, human
  • Il6st protein, mouse
  • Interleukin-6
  • LIF protein, human
  • Leukemia Inhibitory Factor
  • Lif protein, mouse
  • Lymphokines
  • Membrane Glycoproteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Stat3 protein, mouse
  • Trans-Activators
  • Cytokine Receptor gp130
  • Phosphatidylinositol 3-Kinases
  • Mitogen-Activated Protein Kinases