title: Maintenance of the pluripotential phenotype of embryonic stem cells through direct activation of gp130 signalling pathways.
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.
authors.affiliation: Institute for Molecular and Cellular Biology, Osaka University, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yoshida
authors.forename: I
authors.initials: I
authors.lastname: Chambers
authors.forename: J
authors.initials: J
authors.lastname: Nichols
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: M
authors.initials: M
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Yasukawa
authors.forename: M
authors.initials: M
authors.lastname: Shoyab
authors.forename: T
authors.initials: T
authors.lastname: Taga
authors.forename: T
authors.initials: T
authors.lastname: Kishimoto
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D001755:Blastocyst / Q000166:cytology; D002454:Cell Differentiation; D002478:Cells, Cultured; D002678:Chimera; D050822:Cytokine Receptor gp130; D005260:Female; D005786:Gene Expression Regulation; D006131:Growth Inhibitors / Q000494:pharmacology / Q000502:physiology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008222:Lymphokines / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010641:Phenotype; D018121:Receptors, Cytokine / Q000737:chemistry / Q000502:physiology*; D018123:Receptors, Interleukin / Q000737:chemistry / Q000502:physiology*; D019947:Receptors, Interleukin-6; D053606:Receptors, OSM-LIF; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology
chemical_list: D015703:Antigens, CD; D006131:Growth Inhibitors; C494200:Il6st protein, mouse; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; C507838:Lif protein, mouse; C507841:Lifr protein, mouse; D008222:Lymphokines; D008562:Membrane Glycoproteins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D053606:Receptors, OSM-LIF; D050822:Cytokine Receptor gp130