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 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.
Zeng
H
H
Department of Medicine, Division of Hematology, University of Washington, Seattle 98195, USA.
Masuko
M
M
Jin
L
L
Neff
T
T
Otto
K G
KG
Blau
C A
CA
D000818:Animals; D001665:Binding Sites; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D008533:Megakaryocytes / Q000166:cytology; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018121:Receptors, Cytokine; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; D015398:Signal Transduction; D022021:Tacrolimus Binding Proteins / Q000235:genetics; D014162:Transfection; D051941:fms-Like Tyrosine Kinase 3
D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D018121:Receptors, Cytokine; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D053628:Receptors, Thrombopoietin; D011993:Recombinant Fusion Proteins; C084881:flt3 ligand protein; D016179:Granulocyte Colony-Stimulating Factor; C082218:MPL protein, human; C497971:Flt3 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051941:fms-Like Tyrosine Kinase 3; D022021:Tacrolimus Binding Proteins