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The transcription factors STAT5A/B regulate GM-CSF-mediated granulopoiesis.
Blood 114, 4721-4728 (2009)
Neutrophils play a vital role in the immune defense, which is evident by the severity of neutropenia causing life-threatening infections. Granulocyte macrophage-colony stimulating factor (GM-CSF) controls homeostatic and emergency development of granulocytes. However, little is known about the contribution of the downstream mediating transcription factors signal transducer and activator of transcription 5A and 5B (STAT5A/B). To elucidate the function of this pathway, we generated mice with complete deletion of both Stat5a/b genes in hematopoietic cells. In homeostasis, peripheral neutrophils were markedly decreased in these animals. Moreover, during emergency situations, such as myelosuppression, Stat5a/b mutant mice failed to produce enhanced levels of neutrophils and were unable to respond to GM-CSF. Both the GM-CSF permitted survival of mature neutrophils and the generation of granulocytes from granulocyte-macrophage progenitors (GMPs) were markedly reduced in Stat5a/b mutants. GMPs showed impaired colony-formation ability with reduced number and size of colonies on GM-CSF stimulation. Moreover, continuous cell fate analyses by time-lapse microscopy and single cell tracking revealed that Stat5a/b-null GMPs showed both delayed cell-cycle progression and increased cell death. Finally, transcriptome analysis indicated that STAT5A/B directs GM-CSF signaling through the regulation of proliferation and survival genes.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Colony-Stimulating Facotr; physiological negative regulator; hematopoietic stem-cells; factor-receptor; emergency granulopoiesis; lymhoid development; gene-expression; deficient mice; growth-factor; granulocyte
Language
Publication Year
2009
HGF-reported in Year
2009
ISSN (print) / ISBN
0006-4971
e-ISSN
1528-0020
Journal
Blood
Quellenangaben
Volume: 114,
Issue: 21,
Pages: 4721-4728
Publisher
American Society of Hematology
Reviewing status
Peer reviewed
Institute(s)
Institute of Stem Cell Research (ISF)
PSP Element(s)
G-550900-001
Scopus ID
73949103238
PubMed ID
19779039
Erfassungsdatum
2009-12-31