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IMM334 - lecture 2.doc

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University of Toronto St. George

IMM334Fall 2013SECOND LECTURE The problem of marrow maintenanceBlood cell production in marrowrate of productionrate of loss simultaneous maturation and divisionrelease on maturity controlled by expression of cell surface adhesion moleculeslife long process Multiple assembly lines in marrow to produce erthyrocytes platelets neutrophils monocytes eosinophils basophils B cells T cells Where do precursor cells come from Hematopoietic reconstitution1x106 BM cellsirradiated mouseBM blood mouse reconstitutes number of precursor cells back to normal 1x103 BM cellsirradiated mouse45 mice see no reconstitution 15 mice see transient reconstitution 120 mice see PERMANENT reconstitution all lineagesClonal reconstitutions are multilineage both sustained and transient Sustained reconstitutionBMirradiated mousesome sustained reconstitutionthus can be done repeatedlystem cells regenerate whole tissue and also regenerates progeny that remain so fully functional stem cell Visual demonstration of bone marrow reconstitution showsinject single stem cell labelled with transgene luciferate therefore can be detected by lightstem cells localized to site of injection or spread throughout the bodymultiple outcomes difference due to differences in program in cells injected HSC sustain longterm hematopoiesis generate multiple lineages selfrenew sustain selfrenewal over time The stem cell basis of tissue permenanceprecursors come from stem cells are continously replenishedstem cells both selfrenew and differentiate stem cellcommuted precursorsdifferentiating precursorsStem cell clones sustained by selfrenewal To maintain proliferative tissues continuous differentiation and maturation marrow testes gut skin etc until cell leaves anatomical compartment AND cells at the head of the process selfrenew otherwise empty compartmnetRelationship between selfrenewal and clonal fateAt limiting dilution get 3 patterns of reconstitution 1 local undetected in blood or tissuesno detection unless there are a billiion cells in that compartment 2 systemic transient 3 systemic permanent Selfrenewal Stem cellsstem cells and differentiated cellsthis is an example of ASYMMETRIC RENEWAL DIVISION
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