Maintenance of the pluripotential phenotype of embryonic stem cells through direct activation of gp130 signalling pathways

Mech Dev. 1994 Feb;45(2):163-71. doi: 10.1016/0925-4773(94)90030-2.

Abstract

Propagation of the undifferentiated pluripotential phenotype of embryonic stem (ES) cells is dependent on the cytokine differentiation inhibiting activity/leukemia inhibitory factor (DIA/LIF). The DIA/LIF receptor complex is a heterodimer of DIA/LIF receptor (DIA/LIF-R) and gp130. The latter is also a component of the interleukin-6 (IL-6) receptor complex. We report that a combination of IL-6 and soluble IL-6 receptor (sIL-6R), which can induce homodimerisation of gp130 and activation of signalling processes, sustains self-renewal of pluripotential ES cells. Our findings indicate that the IL-6/sIL-6R complex acts on ES cells through gp130 alone, bypassing DIA/LIF-R, and therefore implicate gp130 as the key component in the signalling pathway responsible for stem cell renewal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD*
  • Blastocyst / cytology
  • Cell Differentiation
  • Cells, Cultured
  • Chimera
  • Cytokine Receptor gp130
  • Female
  • Gene Expression Regulation
  • Growth Inhibitors / pharmacology
  • Growth Inhibitors / physiology*
  • Interleukin-6*
  • Leukemia Inhibitory Factor
  • Leukemia Inhibitory Factor Receptor alpha Subunit
  • Lymphokines / pharmacology
  • Lymphokines / physiology*
  • Male
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Phenotype
  • Receptors, Cytokine / chemistry
  • Receptors, Cytokine / physiology*
  • Receptors, Interleukin / chemistry
  • Receptors, Interleukin / physiology*
  • Receptors, Interleukin-6
  • Receptors, OSM-LIF
  • Signal Transduction*
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / physiology

Substances

  • Antigens, CD
  • Growth Inhibitors
  • Il6st protein, mouse
  • Interleukin-6
  • Leukemia Inhibitory Factor
  • Leukemia Inhibitory Factor Receptor alpha Subunit
  • Lif protein, mouse
  • Lifr protein, mouse
  • Lymphokines
  • Membrane Glycoproteins
  • Receptors, Cytokine
  • Receptors, Interleukin
  • Receptors, Interleukin-6
  • Receptors, OSM-LIF
  • Cytokine Receptor gp130