Age- and stage-specific regulation patterns in the hematopoietic stem cellhierarchy

The molecular mechanisms that regulate self-renewal and differentiation of very primitive hematopoietic stem and progenitor cells in vivo are still po orly understood. Despite the clinical relevance, even less is known about t he mechanisms that regulate these cells in old animals. In a forward geneti c approach, using quantitative trait linkage analysis in the mouse BXD reco mbinant inbred set, this study identified loci that regulate the genetic va riation in the size of primitive hematopoietic cell compartments of young a nd old C57BL6 and DBA/2 animals. Linked loci were confirmed through the gen eration and analysis of congenic animals. In addition, a comparative linkag e analysis revealed that the number of primitive hematopoietic cells and he matopoietic stem cells are regulated in a stage-specific and an age-specifi c manner. (C) 2001 by The American Society of Hematology.