Erythropoietic progenitors capable of colony formation in culture: Response of normal and genetically anemic W/Wv mice to manipulations of the erythron

Abstract Changes in the number and erythropoietin sensitivity of erythropoietic progenitor cells (CFU‐E or E) capable of erythropoietin‐dependent colony formation in culture have been measured in mice subjected to a variety of manipulations known to affect erythropoiesis. Injection of erythropoietin into mice whose E levels had been reduced by transfusion‐induced plethora stimulated a striking increase in this population within 24 hours in both spleen and marrow. Following irradiation and marrow transplantation E were found to regenerate in the spleen with a population doubling time of 6 hours. Evidence of erythropoietin‐dependent stimulation of E in vivo under conditions of hemopoietic regeneration was also obtained, although substantial numbers of E were detected in both regenerating spleen and marrow of plethoric mice even without erythropoietin administration, In the same experiments comparable effects of erythropoietin on pluripotent stem cells or the progenitors of granulopoietic colonies in culture were not observed. Detailed studies of the dependence of colony formation on erythropoietin concentration in culture showed variations in erythropoietin sensitivity of E from normal, regenerating and plethoric, erythropoietin‐stim‐ulated spleen and marrow. This finding provides the basis for an extremely fine mechanism regulating the flow of erythropoietic differentiation at the level of the production of E. The number of E present in the marrow of untreated W/W V mice was normal, but their sensitivity to erythropoietin in culture was decreased to a similar extent as E from normal mice exposed to a heightened erythropoietic demand. Plethora had a more marked effect in reducing E numbers in W/W V mice than in +/ + controls and stimulation of E following subsequent erythropoietin administration was highly defective. The results of these studies provide further evidence that cells identified as E represent a stage of differentiation along the erythropoietic pathway that is several steps removed from pluripotent stem cells and support the view that erythropoiesis, granulopoiesis and stem cell self‐renewal are regulated to a major degree by independent mechanisms.