STAT3 is a negative regulator of granulopoiesis but is not required for G-CSF-dependent differentiation.
STAT3 has been described as an essential component of G-CSF-driven cell proliferation and granulopoiesis. This notion was tested by conditional gene ablation in transgenic mice. Contrary to expectation, granulocytes developed from STAT3 null bone marrow progenitors, and STAT3 null neutrophils displayed mature effector functions. Rather than a deficit in granulopoiesis, mice lacking STAT3 in their hematopoietic progenitors developed neutrophilia, and bone marrow cells were hyperresponsive to G-CSF stimulation. These studies provide direct evidence for STAT3-independent granulopoiesis and suggest that STAT3 directs a negative feedback loop necessary for controlling neutrophil numbers, possibly through induced expression of the signaling inhibitor, SOCS3.
Lee
Chien-kuo
CK
Department of Pathology, Kaplan Comprehensive Cancer Center, New York University School of Medicine, 10016, USA.
Raz
Regina
R
Gimeno
Ramon
R
Gertner
Rachel
R
Wistinghausen
Birte
B
Takeshita
Kenichi
K
DePinho
Ronald A
RA
Levy
David E
DE
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009504:Neutrophils / Q000502:physiology; D014176:Protein Biosynthesis; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C491411:Socs3 protein, mouse; C494087:Stat3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D016179:Granulocyte Colony-Stimulating Factor