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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)
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Colony-Stimulating Facotr; physiological negative regulator; hematopoietic stem-cells; factor-receptor; emergency granulopoiesis; lymhoid development; gene-expression; deficient mice; growth-factor; granulocyte
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Zeitschrift Blood
Quellenangaben Band: 114, Heft: 21, Seiten: 4721-4728 Artikelnummer: , Supplement: ,
Verlag American Society of Hematology
Begutachtungsstatus Peer reviewed