Earlier Onset of Hematopoietic Differentiation after Expansion of the Endogenous Stem Cell Pool

In previous studies of growth and differentiation of endogenous hematopoietic spleen colonies (E-CFU), the time of resumption of differentiation after irradiation was increasingly delayed, but the rate of growth of the E-CFU compartment was not affected as the radiation dose was increased. These results suggested that differentiation might not occur until a critical stem cell pool size was attained. To further study this question, mice were injected prior to irradiation with substances which increase the E-CFU compartment; foreign plasma and endotoxin. Mice were injected daily for 4 days with human plasma or once with S. typhosa endotoxin 1 day prior to exposure to 580, 670, 770, 860, or 960 rads, and killed 3 to 10 days after irradiation. Plasma injection hastened the resumption of erythropoiesis, as measured by increased iron uptake, by about 5 days and endotoxin injection by about 3 days. Spleen weight and colony counts also increased earlier in treated mice. For each increment of 100 rads the time of onset of erythropoiesis was delayed an average of 1.5 days. The data are in accord with the concept that onset of differentiation after irradiation is geared to stem cell pool size.