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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 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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Metadata
- 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
- Health Sciences › Medicine › Hematology › 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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