Molecular Signatures of Quiescent, Mobilized and Leukemia-Initiating Hematopoietic Stem Cells 英文参考文献.docVIP

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Molecular Signatures of Quiescent, Mobilized and Leukemia-Initiating Hematopoietic Stem Cells 英文参考文献.doc

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Molecular Signatures of Quiescent, Mobilized and Leukemia-Initiating Hematopoietic Stem Cells 英文参考文献

MolecularSignaturesofQuiescent,Mobilizedand Leukemia-InitiatingHematopoieticStemCells E.CamillaForsberg1.*,EmmanuellePassegue′2.,SusanS.Prohaska3.,AmyJ.Wagers4.,MartinaKoeva1, JoshuaM.Stuart1,IrvingL.Weissman3 1InstituteforBiologyofStemCells,DepartmentofBiomolecularEngineering,UniversityofCaliforniaSantaCruz,SantaCruz,California,UnitedStatesofAmerica,2TheEli andEdytheBroadCenterforRegenerationMedicineandStemCellResearch,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica, 3Institute ofStem CellBiology and Regenerative Medicine,Departments ofPathology and Developmental Biology, Stanford University School ofMedicine, Stanford, California,United StatesofAmerica, 4JoslinDiabetes Center,HarvardStemCellInstitute andDepartment ofStemCellandRegenerativeBiology,HarvardUniversity, Cambridge,Massachusetts,UnitedStatesofAmerica Abstract Hematopoieticstemcells(HSC)arerare,multipotentcellscapableofgeneratingallspecializedcellsofthebloodsystem. Appropriate regulation of HSC quiescence is thought to be crucial to maintain their lifelong function; however, the molecularpathwayscontrollingstemcellquiescenceremainpoorlycharacterized.Likewise,themoleculareventsdriving leukemogenesisremainelusive.Inthisstudy,wecomparethegeneexpressionprofilesofsteady-statebonemarrowHSCto non-self-renewing multipotent progenitors; toHSC treated with mobilizing drugs that expandthe HSC pool andinduce egress from the marrow; and to leukemic HSC in amouse model of chronic myelogenous leukemia. By intersecting the resulting lists of differentially regulated genes we identify a subset of molecules that are downregulated in all three circumstances,andthusmaybeparticularlyimportantforthemaintenanceandfunctionofnormal,quiescentHSC.These resultsidentifypotentialkeyregulatorsofHSCandgiveinsightsintotheclinicallyimportantprocessesofHSCmobilization fortransplantationandleukemicdevelopmentfromcancerstemcells. Citation: Forsberg EC, Passegue′ E, Prohaska SS, Wagers AJ, Koeva M, et al