Aging of the Microenvironment Influences Clonality in Hematopoiesis 英文参考文献.docVIP

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Aging of the Microenvironment Influences Clonality in Hematopoiesis 英文参考文献.doc

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Aging of the Microenvironment Influences Clonality in Hematopoiesis 英文参考文献

AgingoftheMicroenvironmentInfluencesClonalityin Hematopoiesis ViragVas1,KatharinaSenger1,KarinDo¨rr1,AnjaNiebel1,HartmutGeiger1,2* 1DepartmentofDermatologyandAllergicDiseases,UniversityofUlm,Ulm,Germany,2DivisionofExperimentalHematologyandCancerBiology,CincinnatiChildren’s HospitalMedicalCenter,UniversityofCincinnati,Cincinnati,Ohio,UnitedStatesofAmerica Abstract Themechanismsoftheage-associatedexponentialincreaseintheincidenceofleukemiaarenotknownindetail.Leukemia aswellasagingareinitiatedandregulatedinmulti-factorialfashionbycell-intrinsicandextrinsicfactors.Theroleofaging ofthemicroenvironmentforleukemiainitiation/progressionhasnotbeeninvestigatedingreatdetailsofar.Clonalityin hematopoiesis is tightly linked to the initiation of leukemia. Based on a retroviral-insertion mutagenesis approach to generate primitive hematopoietic cells with an intrinsic potential for clonal expansion, we determined clonality of transduced hematopoietic progenitor cells (HPCs) exposed to a young or aged microenvironment in vivo. While HPCs displayedprimarilyoligo-clonalitywithinayoungmicroenvironment,agedanimalstransplantedwithidenticalpoolofcells displayedreducedclonalitywithintransducedHPCs.Ourdatashowthatanagednicheexertsadistinctselectionpressure ondominantHPC-clonesthusfacilitating thetransitiontomono-clonality, whichmightbeoneunderlyingcauseforthe increasedage-associatedincidenceofleukemia. Citation: Vas V, Senger K, Do¨rr K, Niebel A, Geiger H (2012) Aging of the Microenvironment Influences Clonality in Hematopoiesis. PLoS ONE 7(8): e42080. doi:10.1371/journal.pone.0042080 Editor:WolfgangWagner,RWTHAachenUniversityMedicalSchool,Germany ReceivedMarch1,2012;AcceptedJuly2,2012;PublishedAugust6,2012 Copyright:?2012Vasetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermitsunrestricted use,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbygrantsfromtheDeutscheFor