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STAT3 controls myeloid progenitor growth during emergency granulopoiesis
Open accessAbstract
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.
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“granulocyte cell-stimulating factor–mediated activation of STAT3 induces granulocytic progenitor proliferation through transcriptional upregulation of CCAAT/enhancer-binding protein (C/EBP)β and c-Myc”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Zhang et al., 2010
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“AD-HIES patients do not demonstrate quantitative defects in basal or stress hematopoiesis, including the production of neutrophils, total lymphocyte numbers, red blood cells, or platelets”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Zhang et al., 2010
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Metadata
- Authors
- Zhang, H., Nguyen-Jackson, H., Panopoulos, A. D., Li, H. S., Murray, P. J., & Watowich, S. S.
- Affiliations
- The University of Texas MD Anderson Cancer Center (US)
- St. Jude Children's Research Hospital (US)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2010-10-07
- Volume
- 116
- Issue
- 14
- Pages
- 2462-2471
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC2953883
- OpenAlex
- W2041168245
- Semantic Scholar
- 911cf5f012ca2c41275c386f29013395eb9d6499
- Cited by
- 232
- References
- 50
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 11 · 2023: 13 · 2022: 12 · 2021: 17 · 2020: 24 · 2019: 19 · 2018: 12 · 2017: 16 · 2016: 18 · 2015: 12 · 2014: 16 · 2013: 15 · 2012: 13
- FWCI
- 6.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (P30CA16672, T32CA009598, P30CA016672, T32 CA09598-16)
- National Institute of Allergy and Infectious Diseases (R21AI073587, AI073587)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Hematology › Blood disorders and treatments
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- STAT3, emergency granulopoiesis, granulocyte colony-stimulating factor, myeloid progenitor cells, neutrophil production, Listeria monocytogenes infection, C/EBPβ, c-Myc, C/EBPα, cell cycle progression, transcriptional regulation, bone marrow
- MeSH terms
- Animals, Cell Cycle, Gene Expression Regulation, Granulocytes, Hematopoietic Stem Cells, Listeria monocytogenes, Promoter Regions, Genetic, Signal Transduction, Granulocyte Colony-Stimulating Factor, Proto-Oncogene Proteins c-myc, Leukopoiesis, CCAAT-Enhancer-Binding Proteins, CCAAT-Enhancer-Binding Protein-beta, STAT3 Transcription Factor, Mice
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