Quantitative genetic variation in the hematopoietic stem cell and progenitor cell compartment and in lifespan are closely linked at multiple loci in BXD recombinant inbred mice.
The number of bone marrow hematopoietic stem and progenitor cells as defined by the lineage(-), Sca1(++), c-kit(+) (LSK) phenotype and their proliferative capacity in vitro are subject to quantitative genetic variation, and several quantitative trait loci (QTL) have been identified in young mice. Because some traits affecting hematopoiesis also change with age in a mouse strain-dependent fashion, we performed quantitative trait analysis in aged BXD recombinant inbred (RI) mice for the number and frequency of LSK cells, and for their proliferative capacity in vitro. Several novel QTL were identified. The number and frequency of LSK cells in old mice correlated inversely with lifespan. Furthermore, 4 of 7 lifespan QTL overlap with QTL contributing to the number, frequency, or proliferative capacity of LSK cells in young or old mice. Taken together, these data establish a close genetic, and perhaps functional, link between genetic variation in lifespan and characteristics of stem and progenitor cells.
Carl C. Icahn Center for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, Box 1496, One Gustave L. Levy Place, New York, NY 10029, USA.
Els
E
Henckaerts
Jessica C
JC
Langer
Hans-Willem
HW
Snoeck
D000375:Aging / Q000235:genetics*; D000818:Animals; D000067696:Ataxin-1; D000067528:Ataxins; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D019070:Cell Lineage / Q000502:physiology; D008040:Genetic Linkage; D014644:Genetic Variation; D006410:Hematopoiesis / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D019655:Quantitative Trait, Heritable; D011994:Recombinant Proteins / Q000235:genetics
D000067696:Ataxin-1; D000067528:Ataxins; C000593750:Atxn1 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D019009:Proto-Oncogene Proteins c-kit