Differential Regulation of Bone Marrow-Derived Endothelial Progenitor Cells and Endothelial Outgrowth Cells by the Notch Signaling Pathway 英文参考文献.docVIP

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Differential Regulation of Bone Marrow-Derived Endothelial Progenitor Cells and Endothelial Outgrowth Cells by the Notch Signaling Pathway 英文参考文献.doc

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Differential Regulation of Bone Marrow-Derived Endothelial Progenitor Cells and Endothelial Outgrowth Cells by the Notch Signaling Pathway 英文参考文献

DifferentialRegulationofBoneMarrow-Derived EndothelialProgenitorCellsandEndothelialOutgrowth CellsbytheNotchSignalingPathway Jing-YuanChen1.,LeiFeng2.,Hai-LongZhang2.,Jun-ChangLi2.,Xin-WeiYang2,Xiu-LiCao2,LiLiu1, Hong-YanQin2,Ying-MinLiang1*,HuaHan1,2* 1Department of Hematology, Tangdu Hospital, Fourth Military Medical University, Xi’an, People’s Republic of China, 2State Key Laboratory of Cancer Biology, DepartmentofMedicalGeneticsandDevelopmentalBiology,FourthMilitaryMedicalUniversity,Xi’an,People’sRepublicofChina Abstract Endothelialprogenitorcells(EPCs)areheterogeneouspopulationsofcellsthatparticipateinvasculogenesisandpromote tissueregeneration.HoweverthedifferentrolesofEPCpopulationsinvasculogenesisandtissueregeneration,aswellas theirregulationandmechanismsremainelusive.Inthepresentstudy,weculturedbonemarrow(BM)-derivedearlyEPCs (EEPCs)andendothelialoutgrowthcells(EOCs),andinvestigatedtheirrolesinliverregenerationandtheirregulationbythe Notchsignalingpathway.WefoundthatNotchsignalingexhibiteddifferenteffectsontheproliferationandmigrationof EEPCs and EOCs. Our results also showed that while EEPCs failed to form vessel-like structures in a three dimensional sproutingmodelinvitro,EOCscouldsproutandformendothelialcords,andthiswasregulatedbytheNotchsignaling.We further showed that, by using a conditional knockout model of RBP-J (the critical transcription factor mediating Notch signaling), Notch signaling differentially regulates EEPCs and EOCs. In a partial hepatectomy (PHx) model, EEPCs Notch- dependently benefitted liver regeneration with respect to liver function and hepatocyte proliferation and apoptosis. In contrast,EOCsappearednotdirectlyinvolvedintherecoveryofliverfunctionandtheincreaseofhepatocytes.Thesedata suggestedthattheRBP-J-mediatedNotchsignalingdifferentiallyregulatedthetwotypesofEPCs,whichshoweddifferent rolesinliverregeneration. Citation:ChenJ-Y,FengL,ZhangH-L,LiJ-C,YangX-W,etal.(2012)DifferentialRegulationofBoneMarrow-DerivedEndothelialProgenit