Lifelong hematopoiesis in both reconstituted and sublethally irradiated mice is provided by multiple sequentially recruited stem cells

Objective, To evaluate the dynamics of stem cell production to hematopoiesi s, the number of active stem cell clones and the lifespan of individual clo nes were studied. Materials and Methods. The clonal contribution of primitive hematopoietic s tern cells (HSC) responsible for long-term hematopoiesis was determined usi ng two approaches. In one model, irradiated female mice were reconstituted with retrovirally marked male hematopoietic cells. In the second model, mic e were irradiated sublethally without hematopoietic cell transplantation. I n both models, bone marrow cells were serially sampled from the same mouse throughout a 12- to 20-month period and injected into irradiated recipients for analysis of day 10 colony-forming unit-spleen (CFU-S), The donor origi n of CFU-S was determined by the presence of retrovirally marked cells or c ells with chromosomal aberrations, Results. The results of the two essentially different models show that 1) h ematopoiesis is mainly the product of small clones of hematopoietic cells; 2) the lifespan of the majority of clones is only 1 to 2 months; 3) the clo nes usually function locally; and 4) the vast majority of the clones replac e one another sequentially. Primitive HSCs capable of producing long-lived clones (about 10% among all clones), which exist during the entire life of a mouse, were detected by the radiation-marker technique only. Conclusions. Multiple short-living clones (at least on the level of CFU-S p roduction) comprise the vast majority of the active stem tells in transplan ted recipients or after endogenous recovery from sublethal irradiation. (C) 2001 International Society for Experimental Hematology. Published by Elsev ier Science Inc.