Receptor specificity in the self-renewal and differentiation of primary multipotential hemopoietic cells

To determine whether cytokine-induced signals generate unique responses in multipotential hemopoietic progenitor cells, the signaling domains of 3 dif ferent growth factor receptors (MpI, granulocyte-colony-stimulating factor [G-CSF] receptor, and Flt-3) were inserted into mouse primary bone marrow c ells. To circumvent the activation of endogenous receptors, each signaling domain was incorporated into an FK506 binding protein (FKBP) fusion to allo w for its specific activation using synthetic FKBP ligands, Each signaling domain supported the growth of Ba/F3 cells; however, only MpI supported the sustained growth of transduced marrow cells, with a dramatic expansion of multipotential progenitors and megakaryocytes. These findings demonstrate t hat the self-renewal and differentiation of multipotential progenitor cells can be influenced through distinct, receptor-initiated signaling pathways. (C) 2001 by The American Society of Hematology.