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.
Centre for Genome Research, University of Edinburgh, United Kingdom.
J
J
Nichols
I
I
Chambers
A
A
Smith
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