title: A genetic determinant that specifically regulates the frequency of hematopoietic stem cells.
abstract: The regulation of hematopoietic stem cell (HSC) homeostasis is not well understood. We screened for genetic polymorphisms that were linked to differences between mouse strains in the numbers of long-term reconstituting HSCs or restricted progenitors in the bone marrow. AKR/J mice had significantly higher frequencies and numbers of both HSCs and restricted progenitors in their bone marrow than C57BL/Ka-Thy-1.1 mice. The C57BL/Ka-Thy-1.1 alleles were partially dominant. A locus on chromosome 17, including the H-2 complex, was significantly linked to the frequency of long-term self-renewing HSCs but showed no evidence of linkage to the frequency of restricted progenitors. Conversely, a chromosome 1 locus exhibited suggestive linkage to restricted progenitor frequencies but was not linked to HSC frequency. This demonstrates that there are distinct genetic determinants of the frequencies of HSCs and restricted progenitors in vivo. The AKR/J chromosome 17 locus was not sufficient to increase HSC frequencies when bred onto a C57BL background. This suggests that to affect HSC frequencies, the product(s) of this locus likely depend on interactions with unlinked modifying loci.
authors.affiliation: Howard Hughes Medical Institute and Departments of Internal Medicine and Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Morrison
authors.forename: Dalong
authors.initials: D
authors.lastname: Qian
authors.forename: Libuse
authors.initials: L
authors.lastname: Jerabek
authors.forename: Bonnie A
authors.initials: BA
authors.lastname: Thiel
authors.forename: In-Kyung
authors.initials: IK
authors.lastname: Park
authors.forename: Preston S
authors.initials: PS
authors.lastname: Ford
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Kiel
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: Irving L
authors.initials: IL
authors.lastname: Weissman
authors.forename: Michael F
authors.initials: MF
authors.lastname: Clarke
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000096:biosynthesis; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics / Q000276:immunology; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005819:Genetic Markers / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D007958:Leukocyte Count; D008565:Membrane Proteins / Q000096:biosynthesis; D051379:Mice; D008806:Mice, Inbred AKR; D008810:Mice, Inbred C57BL; D011110:Polymorphism, Genetic / Q000276:immunology*; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis; D013045:Species Specificity; D018800:Thy-1 Antigens / Q000096:biosynthesis
chemical_list: D000950:Antigens, Ly; D005819:Genetic Markers; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D018800:Thy-1 Antigens; D019009:Proto-Oncogene Proteins c-kit