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Hypoxia-inducible factor-1 alpha inhibits self-renewal of mouse embryonic stem cells in Vitro via negative regulation of the leukemia inhibitory factor-STAT3 pathway

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dc.contributor.authorJeong, Chul-Ho-
dc.contributor.authorLee, Hyo-Jong-
dc.contributor.authorCha, Jong-Ho-
dc.contributor.authorKim, Jeong Hun-
dc.contributor.authorKim, Kwang Rok-
dc.contributor.authorKim, Ji-Hye-
dc.contributor.authorYoon, Dae-Kwan-
dc.contributor.authorKim, Kyu-Won-
dc.date.accessioned2009-11-26T06:12:28Z-
dc.date.available2009-11-26T06:12:28Z-
dc.date.issued2007-03-16-
dc.identifier.citationJ Biol Chem. 2007 May 4;282(18):13672-9. Epub 2007 Mar 14.en
dc.identifier.issn0021-9258 (Print)-
dc.identifier.urihttp://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17360716-
dc.identifier.urihttp://hdl.handle.net/10371/15960-
dc.description.abstractDuring mammalian embryogenesis, the early embryo grows in a relatively hypoxic environment due to a restricted supply of oxygen. The molecular mechanisms underlying modulation of self-renewal and differentiation of mouse embryonic stem cells (mESCs) under such hypoxic conditions remain to be established. Here, we show that hypoxia inhibits mESC self-renewal and induces early differentiation in vitro, even in the presence of leukemia inhibitory factor (LIF). These effects are mediated by down-regulation of the LIF-STAT3 signaling pathway. Under conditions of hypoxia, hypoxia-inducible factor-1alpha (HIF-1alpha) suppresses transcription of LIF-specific receptor (LIFR) by directly binding to the reverse hypoxia-responsive element located in the LIFR promoter. Ectopic expression and small interference RNA knockdown of HIF-1alpha verified the inhibitory effect on LIFR transcription. Our findings collectively suggest that hypoxia-induced in vitro differentiation of mESCs is triggered, at least in part, by the HIF-1alpha-mediated suppression of LIF-STAT3 signaling.en
dc.language.isoen-
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.subjectAnimalsen
dc.subjectCell Differentiation/drug effects/*physiologyen
dc.subjectCell Hypoxia/physiologyen
dc.subjectCell Proliferation/drug effectsen
dc.subjectEmbryonic Development/physiologyen
dc.subjectEmbryonic Stem Cells/cytology/*metabolismen
dc.subjectGene Expression Regulation, Developmental/drug effects/physiologyen
dc.subjectHypoxia-Inducible Factor 1, alphaen
dc.subjectSubunit/genetics/*metabolism/pharmacologyen
dc.subjectLeukemia Inhibitory Factor/genetics/*metabolismen
dc.subjectMiceen
dc.subjectRNA, Small Interfering/geneticsen
dc.subjectReceptors, OSM-LIF/genetics/metabolismen
dc.subjectResponse Elements/physiologyen
dc.subjectSTAT3 Transcription Factor/genetics/*metabolismen
dc.subjectSignal Transduction/drug effects/*physiologyen
dc.titleHypoxia-inducible factor-1 alpha inhibits self-renewal of mouse embryonic stem cells in Vitro via negative regulation of the leukemia inhibitory factor-STAT3 pathwayen
dc.typeArticleen
dc.contributor.AlternativeAuthor정철호-
dc.contributor.AlternativeAuthor이효종-
dc.contributor.AlternativeAuthor차종호-
dc.contributor.AlternativeAuthor김정훈-
dc.contributor.AlternativeAuthor김광록-
dc.contributor.AlternativeAuthor김지혜-
dc.contributor.AlternativeAuthor윤대관-
dc.contributor.AlternativeAuthor김규원-
dc.identifier.doi10.1074/jbc.M700534200-
Appears in Collections:
College of Medicine/School of Medicine (의과대학/대학원)Ophthalmology (안과학전공)Journal Papers (저널논문_안과학전공)
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