Epigenetic Features of Human Mesenchymal Stem Cells Determine Their Permissiveness for Induction of Relevant Transcriptional Changes by SYT-SSX1 英文参考文献.docVIP

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Epigenetic Features of Human Mesenchymal Stem Cells Determine Their Permissiveness for Induction of Relevant Transcriptional Changes by SYT-SSX1 英文参考文献.doc

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Epigenetic Features of Human Mesenchymal Stem Cells Determine Their Permissiveness for Induction of Relevant Transcriptional Changes by SYT-SSX1 英文参考文献

EpigeneticFeaturesofHumanMesenchymalStemCells DetermineTheirPermissivenessforInductionof RelevantTranscriptionalChangesbySYT-SSX1 LuisaCironi,PaoloProvero,NicolaRiggi,MichalinaJaniszewska,DomizioSuva,Mario-LucaSuva, VincentKindler,IvanStamenkovic* DivisionofExperimentalPathology,InstituteofPathology,CentreHospitalierUniversitaireVaudois,FacultyofBiologyandMedicine,UniversityofLausanne,Lausanne, Switzerland Abstract Background: A characteristic SYT–SSX fusion gene resulting from the chromosomal translocation t(X;18)(p11;q11) is detectable in almost all synovial sarcomas, a malignant soft tissue tumor widely believed to originate from as yet unidentifiedpluripotentstemcells.TheresultingfusionproteinhasnoDNAbindingmotifsbutpossessesprotein-protein interaction domains that are believed to mediate association with chromatin remodeling complexes. Despite recent advancesintheidentificationofmoleculesthatinteractwithSYT-SSXandwiththecorrespondingwildtypeSYTandSSX proteins,themechanismswherebytheSYT-SSXmightcontributetoneoplastictransformationremainunclear.Epigenetic deregulationhasbeensuggestedtobeonepossiblemechanism. Methodology/PrincipalFindings:WeaddressedtheeffectofSYT/SSXexpressiononthetranscriptomeoffourindependent isolatesofprimaryhumanbonemarrowmesenchymalstemcells(hMSC).Weobservedtranscriptionalchangessimilarto the gene expression signature of synovial sarcoma, principally involving genes whose regulation is linked to epigenetic factors, includingimprintedgenes,geneswithtranscriptionstartsiteswithinaCpG islandandchromatinrelatedgenes. Single population analysis revealed hMSC isolate-specific transcriptional changes involving genes that are important for biologicalfunctionsofstemcellsaswellasgenesthatareconsideredtobemolecularmarkersofsynovialsarcomaincluding IGF2,EPHRINS,andBCL2.MethylationstatusanalysisofsequencesattheH19/IGF2imprintedlocusindicatedthatdistinct epigeneticfeaturescharacterizehMSCpopulationsandconditionthetranscriptionaleffectsofSYT-SSXexpre