Epithelial-Mesenchymal Transition in Cells Expanded In Vitro from Lineage-Traced Adult Human Pancreatic Beta Cells 英文参考文献.docVIP

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Epithelial-Mesenchymal Transition in Cells Expanded In Vitro from Lineage-Traced Adult Human Pancreatic Beta Cells 英文参考文献.doc

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Epithelial-Mesenchymal Transition in Cells Expanded In Vitro from Lineage-Traced Adult Human Pancreatic Beta Cells 英文参考文献

Epithelial-MesenchymalTransitioninCellsExpandedIn VitrofromLineage-TracedAdultHumanPancreaticBeta Cells HolgerA.Russ1,PhilippeRavassard2,JulieKerr-Conte3,FrancoisPattou3,ShimonEfrat1* 1Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel, 2Biothechnology and BiotherapyLaboratory,ResearchCenteroftheBrainandSpinalCordInstitute,CNRSUMR7225,INSERMUMRS975,andUniversityPierreandMarieCurie,Ho?pitalPitie′ Salpe?trie`re,Paris,France,3U859DiabetesCellTherapy,UniversityLille-NorddeFrance,Lille,France Abstract Background:In-vitroexpansionoffunctionalbetacellsfromadulthumanisletsisanattractiveapproachforgeneratingan abundantsourceofcellsforbeta-cellreplacementtherapyofdiabetes.Usinggeneticcell-lineagetracingwehaverecently shown that beta cells cultured from adult human islets undergo rapid dedifferentiation and proliferate for up to 16 populationdoublings.Thesecellshaveraisedinterestaspotentialcandidatesforredifferentiationintofunctionalinsulin- producing cells. Previous work has associated dedifferentiation of cultured epithelial cells with epithelial-mesenchymal transition(EMT),andsuggestedthatEMTgeneratescellswithstemcellproperties.Hereweinvestigatedtheoccurrenceof EMTintheseculturesandassessedtheirstemcellpotential. Methodology/Principal Findings: Using cell-lineage tracing we provide direct evidence for occurrence of EMT in cells originatingfrombetacellsinculturesofadulthumanisletcells.Thesecellsexpressmultiplemesenchymalmarkers,aswell asmarkersassociatedwithmesenchymalstemcells(MSC).However,wedonotfindevidencefortheabilityofsuchcells, norofcellsintheseculturesderivedfromanon-beta-cellorigin,tosignificantlydifferentiateintomesodermalcelltypes. Conclusions/Significance: These findings constitute the first demonstration based on genetic lineage-tracing of EMT in culturedadultprimaryhumancells,andshowthatEMTdoesnotinducemultipotencyincellsderivedfromhumanbeta cells. Citation:RussHA,RavassardP,K