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Blood, 15 July 2004, Vol. 104, No. 2, pp. 374-379.
Prepublished online as a Blood First Edition Paper on February 26, 2004; DOI 10.1182/blood-2003-12-4304.
Submitted December 18, 2003
Accepted February 15, 2004
Quantitative genetic variation in the hematopoietic stem and progenitor cell compartment and in life span are closely linked at multiple loci in BXD recombinant inbred mice
Els Henckaerts, Jessica C Langer, and Hans-Willem Snoeck*
Carl C Icahn Center for Gene Therapy and Molecular Medicine, Mount Sinai School of Medicine, New York, NY, USA
* Corresponding author; email: hans.snoeck{at}mssm.edu.
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 life span. Furthermore four of seven life span 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 life span and characteristics of stem and progenitor cells.
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