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1、Downloadedfromgenome.cshlp.orgonAugust11,2018-PublishedbyColdSpringHarborLaboratoryPressPluripotentStemCellsEscapeFromSenescence-AssociatedDNAMethylationChanges11231CarmenM.Koch,KristinaReck,KaifengShao,QiongLin,SylviaJoussen,Patrick41567Ziegler,GudrunWalenda,WolfDrescher,Bert
2、ramOpalka,TobiasMay,Tim41,321Brümmendorf,MartinZenke,TomoŠarić,WolfgangWagner1HelmholtzInstituteforBiomedicalEngineering,RWTHMedicalSchool,Aachen,Germany2InstituteforNeurophysiology,UniversityofCologne,Cologne,Germany3InstituteforBiomedicalEngineering–CellBiology,RWTHMedicalSc
3、hool,Aachen,Germany4DepartmentofOncology,HematologyandStemCellTransplantation,RWTHMedicalSchool,Aachen,Germany5DepartmentforOrthopedics,RWTHMedicalSchool,Aachen,Germany6DepartmentforHematology,WestGermanCancerCenter,UniversityofDuisburg-Essen,Essen,Germany7DepartmentforGeneReg
4、ulationandDifferentiation,HelmholtzCentreforInfectionResearch,Braunschweig,GermanyCorrespondingauthors:WolfgangWagner,M.D.,Ph.D.,HelmholtzInstituteforBiomedicalEngineering,StemCellBiologyandCellularEngineering,RWTHAachenUniversityMedicalSchool,Pauwelsstraße20,52074Aachen,Germa
5、ny,Tel.+49-241-8088611,E-mail:wwagner@ukaachen.de;andTomoŠarić,M.D.,Ph.D.,InstituteforNeurophysiology,UniversityofCologne,RobertKochStr.39,50931Cologne,Germany,Tel.+49-221-478-86686,Fax+49-221-478-3834,E-mail:tomo.saric@uni-koeln.deRunningtitle:PluripotentCellsEscapeSA-DNAmCha
6、ngesKeywords:ReplicativeSenescence,epigenetic,DNAmethylation,mesenchymalstromalcells,irradiation,telomerase,inducedpluripotentstemcells.1Downloadedfromgenome.cshlp.orgonAugust11,2018-PublishedbyColdSpringHarborLaboratoryPressAbstractPluripotentstemcellsevadereplicativesenescen
7、ce,whereasotherprimarycellslosetheirproliferationanddifferentiationpotentialafteralimitednumberofcelldivisions–andthisisaccompaniedbyspecificsenescence-associatedDNAmethylation(SA-DNAm)changes.Here,weinvestigateSA-DNAmchangesinmesenchymalstromalcells(MSC)uponlong-termculture,i
8、rradiation-inducedsenescence,immortalizationandreprogrammingi