Chronic TLR Signaling Impairs the Long-Term Repopulating Potential of Hematopoietic Stem Cells of Wild Type but Not Id1 Deficient Mice.docVIP

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Chronic TLR Signaling Impairs the Long-Term Repopulating Potential of Hematopoietic Stem Cells of Wild Type but Not Id1 Deficient Mice.doc

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Chronic TLR Signaling Impairs the Long-Term Repopulating Potential of Hematopoietic Stem Cells of Wild Type but Not Id1 Deficient Mice

ChronicTLRSignalingImpairstheLong-Term RepopulatingPotentialofHematopoieticStemCellsof WildTypebutNotId1DeficientMice YingZhao1,FloraLing1,2,Hong-ChengWang1,Xiao-HongSun1,2* 1Immunobiology and Cancer Research Program, OklahomaMedical ResearchFoundation, Oklahoma City, Oklahoma, United States of America, 2Departmentof Cell Biology,UniversityofOklahomaHealthSciencesCenter,OklahomaCity,Oklahoma,UnitedStatesofAmerica Abstract Hematopoieticstemcells(HSCs)maintainlife-longbloodsupplybutareinevitablyexposedtovariousinflammatorystimuli, whichhavebeenshowntobeharmfulforHSCintegritybutthemediatorsofthedeleteriouseffectshavenotbeenfully identified. Here, we show that daily injection of mice with 1 mg of LPS for 30 days triggers a storm of inflammatory cytokines. LPSinjection alsostimulatedthetranscription oftheId1geneinHSCsinvivobut notinvitro,suggestingan indirecteffect.TodeterminetheeffectsofLPStreatmentonHSCfunctionandtoevaluatethesignificanceofId1expression, weassesstherepopulatingpotentialofwildtypeandId1deficientmice,whichweresubjectedtoa30dayregimenofLPS treatment.WefoundthatLPScauseddramaticreductioninthelong-termbutnotshort-termrepopulatingactivityofwild typebutnotId1deficientHSC.ThistreatmentalsoledtoincreasesinHSCcounts,decreasesinBrdU-labelretentionand disturbanceofquiescencedetectedbyKi67staininginwildtypebutnotId1deficientmice.Together,itappearsthatId1,at leastinpart,playsaroleinLPS-induceddamageofHSCintegrity. Citation:ZhaoY,LingF,WangH-C,SunX-H(2013)ChronicTLRSignalingImpairstheLong-TermRepopulatingPotentialofHematopoieticStemCellsofWild TypebutNotId1DeficientMice.PLoSONE8(2):e55552.doi:10.1371/journal.pone.0055552 Editor:KevinD.Bunting,EmoryUniversity,UnitedStatesofAmerica ReceivedOctober11,2012;AcceptedDecember23,2012;PublishedFebruary1,2013 Copyright: ? 2013 Zhao et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedth