Assessment of Human Multi-Potent Hematopoietic StemProgenitor Cell Potential Using a Single In Vitro Screening System 英文参考文献.docVIP
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Assessment of Human Multi-Potent Hematopoietic StemProgenitor Cell Potential Using a Single In Vitro Screening System 英文参考文献
AssessmentofHumanMulti-PotentHematopoieticStem/
ProgenitorCellPotentialUsingaSingleInVitro
ScreeningSystem
JulienCalvo1,2,3,4,AissaBenYoucef1,2,3,4,JanBaijer5,Marie-ChristineRouyez6,FrancoisePflumio1,2,3,4*
1CEA, Laboratoire des Cellules Souches He′matopo?¨e′tiques et Leuce′miques, Institut de Radiobiologie Cellulaire et Mole′culaire (IRCM), Fontenay-aux-Roses, France,
2INSERM,UMR967,Fontenay-aux-Roses,France,3Universite′ ParisDiderot,UMR967,SorbonneParisCite′,Fontenay-aux-Roses,France,4Universite′ Paris-Sud,UMR967,
Fontenay-aux-Roses,France,5CEA,IRCM,CytometryService,Fontenay-aux-Roses,France,6INSERM,U1016,Paris,France
Abstract
Hematopoieticstemcellsareresponsibleforthegenerationoftheentirebloodsystemthroughlife.Thischaracteristicrelies
ontheirabilitytoselfrenewandontheirmulti-potentiality.Thusquantificationofthenumberofhematopoieticstemcells
inagivencellpopulationrequirestoshowbothpropertiesinthestudiedcellpopulations.Althoughxenograftsmodelsthat
supporthumanhematopoieticstemcellshavebeendescribed,suchinvivoexperimentalsystemsremainrestrictiveforhigh
throughput screening purposes for example. In this work we developed a conditional tetracycline inducible system
controlling the expression of the human NOTCH ligand Delta-like 1 in the murine stromal MS5 cells. We cultured
hematopoieticimmaturecellsenrichedinprogenitor/stemcellsincontactwithMS5cellsthatconditionallyexpressDelta-
like1,inconditionsdesignedtogeneratemultipotentiallineagedifferentiation.Weshowthatuponinductionorrepression
+
+
of DL1expression during co-culture,human immature CD34 CD382/low(CD45RA2CD90 ) cells canexpress their B,T, NK,
granulo/monocyticanderythroidpotentialsinasinglewell,andatthesinglecelllevel.Wealsodocumenttheinterference
oflowNOTCHactivationwithhumanBandmyelo/erythroidlymphoiddifferentiation.Thissystemrepresentsanoveltoolto
preciselyquantifyhumanhematopoieticimmaturecellswithbothlymphoidandmyeloidpotentials.
Citation:CalvoJ,BenYoucefA,BaijerJ,RouyezM-C,PflumioF(2012)Assessmen
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