Cited by 384Blood disorders and treatmentsNeutrophil, Myeloperoxidase and Oxidative MechanismsImmune cells in cancer

Intrinsic Requirement for Zinc Finger Transcription Factor Gfi-1 in Neutrophil Differentiation

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Hock, Hanno, Hamblen, Melanie J, Rooke, Heather M, Traver, David, Bronson, Roderick T, Cameron, Scott, Orkin, Stuart H·2003·Immunity

Abstract

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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Crossref · 10.1016/s1074-7613(02)00501-0

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39 of 39 references verified0 citation errors · 0 not checkable

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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.”

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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
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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