Pivotal role of granulocyte colony-stimulating factor in the development of progenitors in the common myeloid pathway.
Granulocyte colony-stimulating factor (G-CSF) is the principal cytokine regulating granulopoiesis. G-CSF receptor-deficient mice (G-CSFR-/-) are neutropenic but have only a modest reduction of committed myeloid progenitors. Since it is likely that compensatory mechanisms are induced by the severe neutropenia present in G-CSFR-/- mice, a competitive repopulation assay was performed. These data show that under basal conditions, G-CSF drives nearly all of granulopoiesis through multiple mechanisms. Most importantly, G-CSFR signals regulate the production and/or maintenance of committed-myeloid progenitors. Surprisingly, G-CSFR signals also play a significant role in the regulation of primitive multipotential progenitors in vivo. The contribution of G-CSFR-/- cells to the hematopoietic stem cell compartment is modestly reduced. Moreover, a marked decrease in the contribution of G-CSFR-/- cells to other progenitors in the myeloid pathway, including erythroid and megakaryocytic progenitors, is observed. In contrast, relative to the hematopoietic stem cell compartment, the contribution of G-CSFR-/- cells to the lymphoid lineages is increased. These data suggest that G-CSFR signals may play a role in directing the commitment of primitive hematopoietic progenitors to the common myeloid lineage. Thus, regulation of G-CSF levels may provide a mechanism for directing primitive hematopoietic progenitors into the common myeloid lineage in response to environmental stresses.
Richards
Michael K
MK
Division of Oncology, Department of Medicine, 660 S Euclid Ave, Campus Box 8007, Saint Louis, MO 63110. dlink@im.wustl.edu
Liu
Fulu
F
Iwasaki
Hiromi
H
Akashi
Koichi
K
Link
Daniel C
DC
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016026:Bone Marrow Transplantation; D002452:Cell Count; D018929:Cell Culture Techniques; D002455:Cell Division; D019070:Cell Lineage; D002465:Cell Movement; D015672:Erythroid Precursor Cells / Q000166:cytology; D016179:Granulocyte Colony-Stimulating Factor / Q000502:physiology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology; D051379:Mice; D018345:Mice, Knockout; D023461:Myeloid Progenitor Cells / Q000166:cytology*; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000502:physiology
D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor