Direct In Vivo Cell Lineage Analysis in the Retrorsine and 2AAF Models of Liver Injury after Genetic Labeling in Adult and Newborn Rats 英文参考文献.docVIP

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Direct In Vivo Cell Lineage Analysis in the Retrorsine and 2AAF Models of Liver Injury after Genetic Labeling in Adult and Newborn Rats 英文参考文献.doc

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Direct In Vivo Cell Lineage Analysis in the Retrorsine and 2AAF Models of Liver Injury after Genetic Labeling in Adult and Newborn Rats 英文参考文献

DirectInVivoCellLineageAnalysisintheRetrorsineand 2AAFModelsofLiverInjuryafterGeneticLabelingin AdultandNewbornRats VirginiePichard,DominiqueAubert,NicolasFerry* INSERMU948,Biothe′rapies He′patiques,CHUHotelDieu,Nantes,France Abstract BackgroundsandAims:Whenhepatocyteproliferationisimpaired,liverregenerationproceedsfromthedivisionofnon parenchymalhepatocyteprogenitors.OvalcellsandSmallHepatocyte-likeProgenitorCells(SHPCs)representthetwomost studiedexamplesofsuchepithelialcellswithputativestemcellcapacity.Inthepresentstudywewishedtocomparethe originofSHPCsproliferatingafterretrorsineadministrationtotheoneofovalcellsobservedafter2-Acetyl-Aminofluorene (2-AAF)treatment. Methodology/PrincipalFindings:Weusedretroviral-mediatednlslacZgeneticlabelingofdividingcellstostudythefateof cellsintheliver.Labelingwasperformedeitherinadultratsbeforetreatmentorinnewbornanimals.Labeledcellswere identified and characterised by immunohistochemistry. In adult-labeled animals, labeling was restricted to mature hepatocytes. Retrorsine treatment did not modify the overall number of labeled cells in the liver whereas after 2-AAF administration unlabeled oval cells were recorded and the total number of labeled cells decreased significantly. When labelingwasperformedinnewbornrats,resultsafterretrorsineadministrationwereidenticaltothoseobtainedinadult- labeledrats.Incontrast,inthe2-AAFregimennumerouslabeledovalcellswerepresentandwereabletogeneratenew labeledhepatocytes.Furthermore,wealsoobservedlabeledbiliarytractsin2-AAFtreatedrats. Conclusions:OurresultssronglysuggestthatSHPCsarederivedfromhepatocytesandweconfirmthatSHPCsandoval cellsdonotsharethesameorigin.Wealsoshowthathepaticprogenitorsarelabeledinnewbornratssuggestingfuture directionsforinvivolineagestudies. Citation:PichardV,AubertD,FerryN(2009)DirectInVivoCellLineageAnalysisintheRetrorsineand2AAFModelsofLiverInjuryafterGeneticLabelinginAdult andNewbornRats.PLoSONE4(9):e7267.doi:10.1371/journal.pone.0007267 Editor:ChristosSamakovlis,S