Ectopic PDX-1 Expression Directly Reprograms Human Keratinocytes along Pancreatic Insulin-Producing Cells Fate 英文参考文献.docVIP

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Ectopic PDX-1 Expression Directly Reprograms Human Keratinocytes along Pancreatic Insulin-Producing Cells Fate 英文参考文献.doc

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Ectopic PDX-1 Expression Directly Reprograms Human Keratinocytes along Pancreatic Insulin-Producing Cells Fate 英文参考文献

EctopicPDX-1ExpressionDirectlyReprogramsHuman KeratinocytesalongPancreaticInsulin-ProducingCells Fate MichalMauda-Havakuk1,2.,NaomiLitichever1,2.,ElladChernichovski1,2,OdeliaNakar1,2,EyalWinkler3, RamMazkereth4,ArieOrenstein3,EranBar-Meir3,PhilippeRavassard5,IritMeivar-Levy1 ,Sarah Ferber1,2 * 1ShebaRegenerativeMedicine,StemCellsandTissueEngineeringCenter,ShebaMedicalCenter,Tel-Hashomer,Israel,2DepartmentofHumanGeneticsandMolecular Medicine,SacklerSchoolofMedicine,Tel-AvivUniversity,Tel-Aviv,Israel,3DepartmentofPlasticandReconstructiveSurgery,ShebaMedicalCenter,Tel-Hashomer,Israel, 4AlbertKatzDepartmentofNeonatology,ShebaMedicalCenter,Tel-Hashomer,Israel,5BiotechnologyandBiotherapygroupCentredeRechercheInstitutduCerveauet delaMoelleCNRSUMR7225,INSERMUMRS795,Universite′ PierreetMarieCurie,Paris,France Abstract Background: Cellular differentiation and lineage commitment have previously been considered irreversible processes. However,recentstudieshaveindicatedthatdifferentiatedadultcellscanbereprogrammedtopluripotencyand,insome cases,directlyintoalternatecommittedlineages.However,althoughpluripotentcellscanbeinducedinnumeroussomatic cellsources,itwasthoughtthatinducingalternatecommittedlineagesisprimarilyonlypossibleincellsofdevelopmentally relatedtissues.Here,wechallengethisviewandanalyzewhetherdirectadultcellreprogrammingtoalternatecommitted lineagescancrosstheboundariesofdistinctdevelopmentalgermlayers. Methodology/PrincipalFindings:Weectopicallyexpressednon-integratingpancreaticdifferentiationfactorsinectoderm- derived human keratinocytes to determine whether these factors could directly induce endoderm-derived pancreatic lineageandb-cell-likefunction.WefoundthatPDX-1andtoalesserextentotherpancreatictranscriptionfactors,could rapidly and specifically activate pancreatic lineage and b-cell-like functional characteristics in ectoderm-derived human keratinocytes.Humankeratinocytestransdifferentiatedalongthebcelllineageproducedprocessedandsecretedinsulinin respon