Cytokine receptors and hematopoietic differentiation
Author(s)
Robb, L;
Details
Publication Year 2007-10,Volume 26,Issue #47,Page 6715-6723
Journal Title
ONCOGENE
Publication Type
Journal Article
Abstract
Colony- stimulating factors and other cytokines signal via their cognate receptors to regulate hematopoiesis. In many developmental systems, inductive signalling determines cell fate and, by analogy with this, it has been postulated that cytokines, signalling via their cognate receptors, may play an instructive role in lineage specification in hematopoiesis. An alternative to this instructive hypothesis is the stochastic or permissive hypothesis. The latter proposes that commitment to a particular hematopoietic lineage is an event that occurs independently of extrinsic signals. It predicts that the role of cytokines is to provide nonspecific survival and proliferation signals. In this review, we look at the role of cytokine receptor signalling in hematopoiesis and consider the evidence for both hypotheses. Data from experiments that genetically manipulate receptor gene expression in vitro or in vivo are reviewed. Experiments in which cytokine receptors were installed in multipotential cells showed that, in some cases, stimulation with the cognate ligand could lead to alterations in lineage output. The creation of genetically manipulated mouse strains demonstrated that cytokine receptors are required for expansion and survival of single lineages but did not reveal a role in lineage commitment. We conclude that hematopoietic differentiation involves mainly stochastic events, but that cytokine receptors also have some instructive role.
Publisher
NATURE PUBLISHING GROUP
Keywords
COLONY-STIMULATING FACTOR; MPL-DEFICIENT MICE; LEUKEMIA INHIBITORY FACTOR; ERYTHROPOIETIN RECEPTOR; GROWTH-FACTORS; IN-VIVO; C-MPL; TARGETED DISRUPTION; SIGNAL-TRANSDUCTION; CSF RECEPTOR
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Creation Date: 2007-10-01 12:00:00
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