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dc.contributor.authorGupta, Manoj K.
dc.contributor.authorVethe, Heidrun
dc.contributor.authorSoftic, Samir
dc.contributor.authorRao, Tata Nageswara
dc.contributor.authorWagh, Vilas
dc.contributor.authorShirakawa, Jun
dc.contributor.authorBarsnes, Harald
dc.contributor.authorVaudel, Marc
dc.contributor.authorTakatani, Tomozumi
dc.contributor.authorKahraman, Sevim
dc.contributor.authorSakaguchi, Masaji
dc.contributor.authorMartinez, Rachael
dc.contributor.authorHu, Jiang
dc.contributor.authorBjørlykke, Yngvild
dc.contributor.authorRæder, Helge
dc.contributor.authorKulkarni, Rohit N.
dc.date.accessioned2021-05-04T09:32:00Z
dc.date.available2021-05-04T09:32:00Z
dc.date.created2020-11-25T13:44:26Z
dc.date.issued2020
dc.PublishedStem Cell Reports. 2020, 15 (5), 1067-1079.
dc.identifier.issn2213-6711
dc.identifier.urihttps://hdl.handle.net/11250/2753443
dc.description.abstractThe role of leptin receptor (OB-R) signaling in linking pluripotency with growth and development and the consequences of dysfunctional leptin signaling on progression of metabolic disease is poorly understood. Using a global unbiased proteomics approach we report that embryonic fibroblasts (MEFs) carrying the db/db mutation exhibit metabolic abnormalities, while their reprogrammed induced pluripotent stem cells (iPSCs) show altered expression of proteins involved in embryonic development. An upregulation in expression of eukaryotic translation initiation factor 4e (Eif4e) and Stat3 binding to the Eif4e promoter was supported by enhanced protein synthesis in mutant iPSCs. Directed differentiation of db/db iPSCs toward the neuronal lineage showed defects. Gene editing to correct the point mutation in db/db iPSCs using CRISPR-Cas9, restored expression of neuronal markers and protein synthesis while reversing the metabolic defects. These data imply a direct role for OB-R in regulating metabolism in embryonic fibroblasts and key developmental pathways in iPSCs.en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/deed.no*
dc.titleLeptin receptor signaling regulates protein synthesis pathways and neuronal differentiation in pluripotent stem cellsen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2020 The Authorsen_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doi10.1016/j.stemcr.2020.10.001
dc.identifier.cristin1852248
dc.source.journalStem Cell Reportsen_US
dc.source.4015
dc.source.145
dc.source.pagenumber1067-1079en_US
dc.identifier.citationStem Cell Reports. 2020, 15(5), 1067-1079en_US
dc.source.volume15en_US
dc.source.issue5en_US


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