Genetically determined variation in the number of phenotypically defined hematopoietic progenitor and stem cells and in their response to early-acting cytokines
| Autor: | Gary Van Zant, Els Henckaerts, Hans-Willem Snoeck, Patricia Rebollo, Hartmut Geiger, Jessica C. Langer |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
BONE-MARROW Cellular differentiation Immunology Congenic Locus (genetics) Stem cell factor Quantitative trait locus Biology Biochemistry Colony-Forming Units Assay Mice FUNCTIONAL-CHARACTERIZATION Species Specificity MOUSE STRAINS Animals Progenitor cell IN-VIVO KINETICS Crosses Genetic Genetics Stem Cell Factor Science & Technology C-MPL Genetic Variation Membrane Proteins ALLOPHENIC MICE Cell Biology Hematology Hematopoietic Stem Cells Recombinant Proteins Cell biology Hematopoiesis Mice Inbred C57BL Haematopoiesis Phenotype Thrombopoietin Mice Inbred DBA PATTERNS POPULATIONS Cytokines Female Stem cell MOBILIZATION Life Sciences & Biomedicine Cell Division |
| Zdroj: | Blood. 99(11) |
| ISSN: | 0006-4971 |
| Popis: | Quantitative trait analysis may shed light on mechanisms regulating hematopoiesis in vivo. Strain-dependent variation existed among C57BL/6 (B6), DBA/2, and BXD recombinant inbred mice in the responsiveness of primitive progenitor cells to the early-acting cytokines kit ligand, flt3 ligand, and thrombopoietin. A significant quantitative trait locus was found on chromosome 2 that could not be confirmed in congenic mice, however, probably because of epistasis. Because it has been shown that alleles of unknown X-linked genes confer a selective advantage to hematopoietic stem cells in vivo in humans and in cats, we also analyzed reciprocal male D2B6F1 and B6D2F1 mice, revealing an X-linked locus regulating the responsiveness of progenitor and stem cells to early-acting factors. Among DBA/2, B6, and BXD recombinant inbred mice, correlating genetic variation was found in the absolute number and frequency of Lin(-)Sca1(++)kit(+) cells, which are highly enriched in hematopoietic progenitor and stem cells, and in the number of Lin(-)Sca1(++)kit(-) cells, a population whose biologic significance is unknown, suggesting that both populations are functionally related. Suggestive quantitative trait loci (QTLs) for the number of Lin(-)Sca1(++) cells on chromosomes 2, 4, and 7 were confirmed in successive rounds of mapping. The locus on chromosome 2 was confirmed in congenic mice. We thus demonstrated genetic variation in the response to cytokines critical for hematopoiesis in vivo and in the pool size of cells belonging to a phenotype used to isolate essentially pure primitive progenitor and stem cells, and we identified loci that may be relevant to the regulation of hematopoiesis in steady state. ispartof: BLOOD vol:99 issue:11 pages:3947-3954 ispartof: location:United States status: published |
| Databáze: | OpenAIRE |
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