Activin A: a commitment factor in erythroid differentiation.

Erythropoietin is known to be an essential hemopoietic growth factor for maturation of erythroid progenitor cells. Like other hemopoietic growth factors, erythropoietin acts as a survival factor that supports maturation of the erythroid progenitor through the suppression of apoptosis. It is unclear whether erythropoietin can also induce differentiation, or if another external regulator is needed to initiate this process. The present study using murine cell lines revealed that maturation of the erythroid lineage requires costimulation by activin A and erythropoietin. Erythropoietin alone dose not induce differentiation and cells stimulated by activin A alone undergo apoptotic death. Costimulation with erythropoietin and activin A, however, rescues the cells from apoptotic death and permits differentiation. Two-step cultivation showed that cells pretreated with activin A no longer need activin A and differentiate in the presence of erythropoietin alone. The action of activin A commits the cell to death or to differentiation, and the presence of erythropoietin enables differentiation through suppression of apoptosis.