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Blood, 15 July 2001, Vol. 98, No. 2, pp. 328-334
HEMATOPOIESIS
Receptor specificity in the self-renewal and
differentiation of primary multipotential hemopoietic cells
Hui Zeng,
Masayoshi Masuko,
Liqing Jin,
Tobias Neff,
Kevin G. Otto, and
C. Anthony Blau
From the Department of Medicine, Division of
Hematology, University of Washington, Seattle.
To determine whether cytokine-induced signals generate unique
responses in multipotential hemopoietic progenitor cells, the signaling
domains of 3 different growth factor receptors (Mpl, granulocyte-colony-stimulating factor [G-CSF] receptor, and Flt-3) were inserted into mouse primary bone marrow cells. To circumvent the
activation of endogenous receptors, each signaling domain was
incorporated into an FK506 binding protein (FKBP) fusion to allow for
its specific activation using synthetic FKBP ligands. Each signaling
domain supported the growth of Ba/F3 cells; however, only Mpl supported
the sustained growth of transduced marrow cells, with a dramatic
expansion of multipotential progenitors and megakaryocytes. These
findings demonstrate that the self-renewal and differentiation of
multipotential progenitor cells can be influenced through distinct, receptor-initiated signaling pathways.
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