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Blood, 15 August 2000, Vol. 96, No. 4, pp. 1374-1379
HEMATOPOIESIS
Distinct functional properties of highly purified hematopoietic
stem cells from mouse strains differing in stem cell numbers
Gerald de Haan,
Stephen J. Szilvassy,
Todd E. Meyerrose,
Bert Dontje,
Barry Grimes, and
Gary Van
Zant
From the Department of Cell Biology, University of
Groningen, the Netherlands; Division of Hematology/Oncology, Blood and
Marrow Transplant Program, Lucille P. Markey Cancer Center, and
Department of Physiology, University of Kentucky Medical Center,
Lexington, KY.
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-forming cell (CAFC) assay using unfractionated marrow.
To study the nature of this difference, we have now compared the
proliferative fate of single, highly enriched
Sca-1+c-kit+Lin
stem cells from these strains. Although equal in frequency, functional comparison revealed that
Sca-1+c-kit+Lin
cells from DBA mice contained twice as many cells with CAFC activity. DBA clones persisted much longer in vitro, and developed later in time.
To assess 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 recovered 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 genetically determined quantitative and qualitative differences in stem cell behavior likely contribute to the dramatically different hematopoietic recovery rates observed in human transplant patients.

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