Distinct functional properties of highly purified hematopoietic stem cellsfrom mouse strains differing in stem cell numbers

We have previously demonstrated that young adult DBA/2 (DBA) mice have more stem cells than C57BL/6 (B6) mice, as measured in a cobblestone area-formi ng cell (CAFC) assay using unfractionated marrow. To study the nature of th is difference, we have now compared the proliferative fate of single, highl y enriched Sca-1(+)c-kit(+)Lin(-) stem cells from these strains. Although e qual in frequency, functional comparison revealed that Sca-1(+)c-kit(+)Lin( -) cells from DBA mice contained twice as many cells with CAFC activity, DB A clones persisted much longer in vitro, and developed later in time. To as sess whether these differences were of any functional relevance in vivo, we compared engraftment of lethally irradiated mice transplanted with 1000 B6 or DBA Sca-1(+)c-kit(+)Lin(-) cells. Recipients of enriched DBA cells reco vered much faster than animals transplanted with B6 cells. We also studied endogenous hematopoietic recovery after 5-fluorouracil (5-FU) treatment in vivo. Progenitors and peripheral blood cells recovered twice as fast in DBA mice. Thus, DBA stem cells have superior proliferative potential compared with phenotypically identical stem cells obtained from B6 mice. Such geneti cally determined quantitative and qualitative differences in stem cell beha vior likely contribute to the dramatically different hematopoietic recovery rates observed in human transplant patients. (Blood. 2000; 96:1374-1379) ( C) 2000 by The American Society of Hematology.