Derivation of germline competent embryonic stem cells with a combination of interleukin-6 and soluble interleukin-6 receptor.
In this report we document the derivation of pluripotential embryonic stem (ES) cells in the absence of a feeder layer by supplementation of culture media with either ciliary neurotrophic factor or oncostatin M, or with a combination of interleukin-6 (IL-6) plus soluble interleukin-6 receptor (sIL-6R). These factors all activate gp130-associated signaling processes, as does the previously characterized ES cell maintenance factor Differentiation Inhibiting Activity (Leukemia Inhibitory Factor). In particular, the IL-6/sIL-6R complex is thought to act exclusively through gp130. All ES cell lines derived using IL-6/sIL-6R contributed extensively to chimeras and were transmitted through the germline at high frequency. These findings point to a pivotal role for gp130 in ES cell propagation and may be relevant to attempts to derive ES cells from species other than mouse.
Nichols
J
J
Centre for Genome Research, University of Edinburgh, United Kingdom.
Chambers
I
I
Smith
A
A
D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000187:drug effects; D002678:Chimera; D020934:Ciliary Neurotrophic Factor; D016895:Culture Media, Serum-Free; D046508:Culture Techniques / Q000379:methods; D004624:Embryo Transfer; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D053683:Oncostatin M; D010052:Ovariectomy; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D018123:Receptors, Interleukin / Q000502:physiology*; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects
D020934:Ciliary Neurotrophic Factor; D016895:Culture Media, Serum-Free; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D009419:Nerve Tissue Proteins; C508351:OSM protein, human; C508352:Osm protein, mouse; D010455:Peptides; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D011994:Recombinant Proteins; D053683:Oncostatin M