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Kimura, A.* ; Rieger, M. ; Simone, J.M.* ; Chen, W.P.* ; Wickre, M.C.* ; Zhu, B.M.* ; Hoppe, P.S. ; O'Shea, J.J.* ; Schroeder, T. ; Hennighausen, L.*

The transcription factors STAT5A/B regulate GM-CSF-mediated granulopoiesis.

Blood 114, 4721-4728 (2009)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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 Article Number: , Supplement: ,
Publisher American Society of Hematology
Reviewing status Peer reviewed
PSP Element(s) G-550900-001
Scopus ID 73949103238
PubMed ID 19779039
Erfassungsdatum 2009-12-31