Cellular Senescence Ex Vivo p53-Dependent Asymmetric Cell Kinetics英文文献资料.docVIP

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Cellular Senescence Ex Vivo p53-Dependent Asymmetric Cell Kinetics英文文献资料.doc

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Cellular Senescence Ex Vivo p53-Dependent Asymmetric Cell Kinetics英文文献资料

JournalofBiomedicineandBiotechnology?1:1(2001)28–37 ?PII.S1110724301000079? RESEARCH ARTICLE Cellularsenescence:exvivop53-dependent asymmetriccellkinetics PatriziaB.Stadler, JonathanT.Boyd, LakshmiRambhatla,1? ShirleyA.Bohn,1 1 2 Ronald A. Coss, and James L. Sherley1? 3 1 The Molecular Oncology Group, Division of Medical Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA Pharmacology Department, Division of Medical Science, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA Department of Radiation Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA 2 3 Althoughsenescenceisade?ningpropertyofeuploidmammaliancells,itsphysiologicbasisremainsobscure.Previously,cellkinetics propertiesofnormaltissuecellshavenotbeenconsideredinmodelsforsenescence.Wenowprovideevidencethatsenescenceisin factthenaturalconsequenceofnormalinvivosomaticstemcellkineticsextendedinculture.Thisconceptofsenescenceisbased onourdiscoverythatcellsengineeredtoconditionallyexpressthewell-recognizedtumorsuppressorproteinandsenescencefactor, p53,exhibitasymmetriccellkinetics.Invivo,asymmetriccellkineticsareessentialformaintenanceofsomaticstemcells;exvivo ,the samecellkineticsyieldsenescenceasasimplekineticendpoint.Thisnew“asymmetriccellkineticsmodel”forsenescencesuggests novelstrategiesfortheisolationandpropagationofsomatictissuestemcellsinculture. INTRODUCTION During asymmetric kinetics, cell divisions yield one daughter cell that is a long-lived dividing cell like its par- entcell.Theotherdaughteristheprogenitorofacelllineage whoseconstituentsmatureintodifferentiatedcellsthatun- dergoterminalcellcyclearrest.Whencycling,thecellsinthis lineagearecalledtransitcells;intheirmaturearrestedstate theyarecalledterminalcells[21,22].Asymmetriccellkinet- icsareessentialforthefunctionofsomatictissuestemcells. Itallowsthemtomaintainarelativeconstantfractionintheir respectivetissueandpreservelong-