Intrinsic Requirement for Zinc Finger Transcription Factor Gfi-1 in Neutrophil Differentiation
Open accessAbstract
We report essential roles of zinc finger transcription factor Gfi-1 in myeloid development. Gene-targeted Gfi-1(-/-) mice lack normal neutrophils and are highly susceptible to abscess formation by gram-positive bacteria. Arrested, morphologically atypical, Gr1(+)Mac1(+) myeloid cells expand with age in the bone marrow. RNAs encoding primary but not secondary or tertiary neutrophil (granulocyte) granule proteins are expressed. The atypical Gr1(+)Mac1(+) cell population shares characteristics of both the neutrophil and macrophage lineages and exhibits phagocytosis and respiratory burst activity. Reexpression of Gfi-1 in sorted Gfi-1(-/-) progenitors ex vivo rescues neutrophil differentiation in response to G-CSF. Thus, Gfi-1 not only promotes differentiation of neutrophils but also antagonizes traits of the alternate monocyte/macrophage program.
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Two GMP regulatory states were demarcated by transcription factors involved in granulocyte (Cebpe, Gfi1) or monocyte (Irf8, Klf4) specification.
“Two were demarcated by TFs involved in granulocyte (e.g., Cebpe, Gfi1) or monocyte (e.g., Irf8, Klf4) specification10–12,22.”
From Single-cell analysis of mixed-lineage states leading to a binary cell fate choice (2016) · cites this paper as [12]
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- Authors
- Hock, H., Hamblen, M. J., Rooke, H. M., Traver, D., Bronson, R. T., Cameron, S., & Orkin, S. H.
- Affiliations
- Harvard University (US)
- Howard Hughes Medical Institute (US)
- Tufts University (US)
- Corresponding author
- Orkin, Stuart H
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2003-01
- Volume
- 18
- Issue
- 1
- Pages
- 109-120
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W2000355031
- Cited by
- 384
- References
- 39
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 9 · 2023: 18 · 2022: 11 · 2021: 15 · 2020: 14 · 2019: 17 · 2018: 10 · 2017: 22 · 2016: 22 · 2015: 12 · 2014: 12 · 2013: 19 · 2012: 25
- FWCI
- 10.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- GFI1, zinc finger transcription factor, granulocytic differentiation, myeloid development, granulopoiesis, granulocyte colony-stimulating factor, phagocytosis, respiratory burst, bone marrow
- MeSH terms
- Animals, B-Lymphocytes, Bacterial Infections, Bone Marrow Cells, Cell Differentiation, DNA-Binding Proteins, Growth Disorders, Macrophages, Models, Biological, Neutrophils, Phagocytosis, Phenotype, T-Lymphocytes, Transcription Factors, Zinc Fingers, Respiratory Burst, Mice, Knockout, Mice
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