Is erythropoietin the only factor which regulates late erythroid differentiation?

Haematopoiesis is a useful model system for studying differentiation and the regulation of precursor cell populations intermediate between the multipotential stem cell and terminally differentiated end cells. For many years, erythropoietin (Epo) was recognized as the hormone which controls red cell production in vivo. Although other substances are now known to be required during the initial stages of erythropoiesis, late erythroid differentiation is regarded as strictly Epo-dependent. This concept is supported by the recent demonstration that the addition of Epo alone to serum-free bone marrow cell cultures is sufficient to stimulate the CFU-E (colony-forming unit-erythroid-a late erythroid precursor cell approximating to a proerythroblast) to complete differentiation into mature erythrocytes. However, the data reported here indicate that mature erythroid colonies (indistinguishable from those formed by CFU-E + Epo) are formed when adult bone marrow cells are grown for 2 d in methyl cellulose cultures containing spleen cell-conditioned medium (SCM) but no added EPO. SCM is a rich source of growth factors and initial observations suggested that its 'Epo-like' activity could be attributed to: (1) Epo, or (2) a factor which enhances the activity of small amounts of Epo in the culture medium, or (3) a factor(s) distinct from Epo which is also capable of stimulating late erythroid differentiation. The experiments reported here, which include a partial characterization of the 'Epo-like' activity, support the latter interpretation.