Patterns of Proliferation and Differentiation of Hematopoietic Stem Cells After Compartment Depletion

The time of onset and rate of self-replication in the irradiation depleted pluripotential hematopoietic stem cell compartment of mice was measured by a split-dose irradiation method. Mice were irradiated to reduce the compartment size and at daily intervals thereafter were again irradiated; 10 days after the second irradiation the number of endogenous spleen colonies was determined. As irradiation interval was lengthened, colonies increased in an exponential fashion with no apparent lag interval after the first irradiation. The doubling time of the colony-forming cell compartment was calculated as 16 hr if severely reduced in size by 300 R or more but was slower if less irradiation was given. The time of resumption of erythropoiesis following irradiation was measured after 100-900 R by determining uptake of radioactive iron into marrow, spleen, and circulating red cells each day after irradiation. With 200 R or less, erythropoiesis was not abolished. With higher doses there was an interval of no apparent erythropoiesis which increased by 1.6 days for each increment of 100 R. These results are compatible with a pluripotential stem cell compartment, which (1) begins self replication almost immediately following compartment size reduction, and (2) will not differentiate if reduced in size below approximately 10% of normal.