Granulocyte colony-stimulating factor (G-CSF) mediates "emergency" 
granulopoiesis during infection, a process that is mimicked by clinical G-CSF 
use, yet we understand little about the intracellular signaling cascades that 
control demand-driven neutrophil production. Using a murine model with 
conditional deletion of signal transducer and activator of transcription 3 
(STAT3) in bone marrow, we investigated the cellular and molecular mechanisms of 
STAT3 function in the emergency granulopoiesis response to G-CSF administration 
or infection with Listeria monocytogenes, a pathogen that is restrained by G-CSF 
signaling in vivo. Our results show that STAT3 deficiency renders hematopoietic 
progenitor cells and myeloid precursors refractory to the growth-promoting 
functions of G-CSF or L monocytogenes infection. STAT3 is necessary for 
accelerating granulocyte cell-cycle progression and maturation in response to 
G-CSF. STAT3 directly controls G-CSF-dependent expression of 
CCAAT-enhancer-binding protein β (C/EBPβ), a crucial factor in the emergency 
granulopoiesis response. Moreover, STAT3 and C/EBPβ coregulate c-Myc through 
interactions with the c-myc promoter that control the duration of C/EBPα 
occupancy during demand-driven granulopoiesis. These results place STAT3 as an 
essential mediator of emergency granulopoiesis by its regulation of 
transcription factors that direct G-CSF-responsive myeloid progenitor expansion.