title: The differential activation of intracellular signaling pathways confers the permissiveness of embryonic stem cell derivation from different mouse strains.
abstract: The requirement of leukemia inhibitory factor (LIF) for the establishment and maintenance of mouse embryonic stem cells (ESCs) depends on the genetic background of the ESC origin. To reveal the molecular basis of the strain-dependent function of LIF, we compared the activation of the intracellular signaling pathways downstream of LIF in ESCs with different genetic backgrounds. We found that the JAK-Stat3 pathway was dominantly activated in ESCs derived from 'permissive' mouse strains (129Sv and C57BL6), whereas the MAP kinase pathway was hyperactivated in ESCs from 'non-permissive' strains (NOD, CBA and FVB). Artificial activation of Stat3 supported stable self-renewal of ESCs from non-permissive strains. These data suggest that the difference in the balance between the two intracellular signaling pathways underlies the differential response to LIF.
authors.affiliation: Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology (CDB), Minatojima-minamimachi 2-2-3, Chuo-Ku, Kobe 650-0047, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ohtsuka
authors.affiliation: Laboratory for Pluripotent Stem Cell Studies, RIKEN Center for Developmental Biology (CDB), Minatojima-minamimachi 2-2-3, Chuo-Ku, Kobe 650-0047, Japan CREST (Core Research for Evolutional Science and Technology), Japan Science Technology Agency, Honcho 4-1-8, Kawaguchi, Saitama 332-0012, Japan Laboratory for Development and Regenerative Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunokicho, Chuo-ku, Kobe 6500017, Japan niwa@cdb.riken.jp.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Niwa
mesh_terms: D000818:Animals; D017931:DNA Primers / Q000235:genetics; D053595:Embryonic Stem Cells / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D053613:Janus Kinase 1 / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D060888:Real-Time Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013045:Species Specificity
chemical_list: D017931:DNA Primers; D053605:Leukemia Inhibitory Factor; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1
keywords: Embryonic stem cell; LIF signaling; MAP kinase; Signal responsiveness; Stat3