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1、TISSUE-SPECIFICSTEMCELLSp53DirectlyRepressesId2toInhibittheProliferationofNeuralProgenitorCellsa,ba,caa,bBRENTONR.PAOLELLA,MATTHEWC.HAVRDA,AKIOMANTANI,CHRISTINAM.WRAY,a,ca,b,cZHONGHUAZHANG,MARKA.ISRAELabcNorrisCottonCancerCenter,DepartmentofGenetics,andDepartmento
2、fPediatrics,DartmouthMedicalSchool,Hanover,NewHampshire,USAKeyWords.p53genes•Id2genes•Stemcell•CellproliferationABSTRACT(2/2)Neuralprogenitorcells(NPCs)havethecapacitytoprolif-typeNPCsphenocopiesthebehaviorofp53NPCsbyerateandgiverisetoallmajorcentralnervoussystemc
3、ellenhancingNPCproliferationandself-renewal.Interest-typesandrepresentapossiblecelloforiginingliomagene-ingly,p53directlybindstoaconservedsitewithintheId2sis.DeletionofthetumorsuppressorgeneTp53(p53)promotertomediatetheseeffects.Finally,wehaveidenti-resultsinincre
4、asedproliferationandself-renewalofNPCsfiedelevatedId2expressioningliomacelllineswithandisacommongeneticmutationfoundinglioma.Wemutatedp53anddemonstratedthatconstitutiveexpressionhaveidentifiedinhibitorofDNAbinding2(Id2)asanovelofId2playsakeyroleintheproliferationofg
5、liomastem-targetgenedirectlyrepressedbyp53tomaintainnormallikecells.ThesefindingsindicatethatId2functionsasa(2/2)NPCproliferation.p53NPCsexpresselevatedlevelsproproliferativegenethatantagonizesp53-mediatedcellofId2andsuppressionofId2expressionissufficienttoin-cycler
6、egulationinNPCsandmaycontributetothemalig-hibittheincreasedproliferationandself-renewalwhichnantproliferationofglioma-derivedtumorstemcells.resultsfromp53loss.ElevatedexpressionofId2inwild-STEMCELLS2011;29:1090–1101Disclosureofpotentialconflictsofinterestisfoundatt
7、heendofthisarticle.WehavestudiedtheeffectofTp53(p53)pathwaydisrup-INTRODUCTIONtioninNPCs.p53inactivationisthoughttobeanearlyeventingliomagenesis[12]andisestimatedtooccurin87%ofNeuralprogenitorcells(NPCs)residinginthesubventricularsuchtumors[13].Inheritedgermlinemu
8、tationswithinthep53zone(SVZ)ofadultmammalshavetheabilitytogiverisetogene,asseeninpatientswithLi-Fraumenisyndrome,resultallthreemajorcentralnervoussystem
