An autocrine role for erythropoietin in mouse hematopoietic cell differentiation.

Erythropoietin (epo) is the primary regulator of the rate of red blood cell formation in mammals. Because it is formed in the kidney and acts on the bone marrow, its action is classically endocrine. We have shown by PCR that marrow cells contain epo mRNA and that antisense oligodeoxynucleotides, to both epo and its receptor, act on multipotent hematopoietic cells to cause a decrease in mixed erythroid:nonerythroid colonies. The antisense oligonucleotides also cause an increase in mixed nonerythroid colonies with no effect on erythroid burst formation. Sense oligonucleotides have no effect. The antisense suppression is not due to adherent cells, cycling late differentiated cells or lymphocytes, and not reversed by exogenous epo. We conclude that normal erythroid differentiation may have an early phase that is dependent on an internal autocrine mechanism involving epo and its receptor.