| First Author | Zhang H | Year | 2010 |
| Journal | Blood | Volume | 116 |
| Issue | 14 | Pages | 2462-71 |
| PubMed ID | 20581311 | Mgi Jnum | J:165887 |
| Mgi Id | MGI:4838726 | Doi | 10.1182/blood-2009-12-259630 |
| Citation | Zhang H, et al. (2010) STAT3 controls myeloid progenitor growth during emergency granulopoiesis. Blood 116(14):2462-71 |
| abstractText | 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 beta (C/EBPbeta), a crucial factor in the emergency granulopoiesis response. Moreover, STAT3 and C/EBPbeta coregulate c-Myc through interactions with the c-myc promoter that control the duration of C/EBPalpha 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. |
