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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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B-Lymphocytes / cytology
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Bacterial Infections / etiology
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Bone Marrow Cells / cytology
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Bone Marrow Cells / immunology
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Bone Marrow Cells / physiology
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Cell Differentiation / physiology
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology*
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Growth Disorders / etiology
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Macrophages / cytology
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Macrophages / immunology
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Macrophages / physiology
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Mice
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Mice, Knockout
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Models, Biological
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Neutrophils / cytology
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Neutrophils / immunology
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Neutrophils / physiology*
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Phagocytosis
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Phenotype
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Respiratory Burst
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T-Lymphocytes / cytology
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Zinc Fingers / genetics
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Zinc Fingers / physiology
Substances
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DNA-Binding Proteins
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Gfi1 protein, mouse
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Transcription Factors