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
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens, CD*
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Blastocyst / cytology
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Cell Differentiation
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Cells, Cultured
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Chimera
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Cytokine Receptor gp130
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Female
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Gene Expression Regulation
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Growth Inhibitors / pharmacology
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Growth Inhibitors / physiology*
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Interleukin-6*
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Leukemia Inhibitory Factor
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Leukemia Inhibitory Factor Receptor alpha Subunit
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Lymphokines / pharmacology
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Lymphokines / physiology*
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Male
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred C57BL
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Molecular Sequence Data
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Phenotype
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Receptors, Cytokine / chemistry
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Receptors, Cytokine / physiology*
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Receptors, Interleukin / chemistry
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Receptors, Interleukin / physiology*
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Receptors, Interleukin-6
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Receptors, OSM-LIF
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Signal Transduction*
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Stem Cells / cytology*
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Stem Cells / drug effects
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Stem Cells / physiology
Substances
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Antigens, CD
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Growth Inhibitors
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Il6st protein, mouse
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Interleukin-6
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Leukemia Inhibitory Factor
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Leukemia Inhibitory Factor Receptor alpha Subunit
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Lif protein, mouse
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Lifr protein, mouse
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Lymphokines
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Membrane Glycoproteins
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Receptors, Cytokine
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Receptors, Interleukin
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Receptors, Interleukin-6
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Receptors, OSM-LIF
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Cytokine Receptor gp130