Maintenance of the pluripotential phenotype of embryonic stem cells through direct activation of gp130 signalling pathways.
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.
Yoshida
K
K
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Chambers
I
I
Nichols
J
J
Smith
A
A
Saito
M
M
Yasukawa
K
K
Shoyab
M
M
Taga
T
T
Kishimoto
T
T
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
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