Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation.
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.
Hock
Hanno
H
Division of Hematology/Oncology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Hamblen
Melanie J
MJ
Rooke
Heather M
HM
Traver
David
D
Bronson
Roderick T
RT
Cameron
Scott
S
Orkin
Stuart H
SH
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology; D001424:Bacterial Infections / Q000209:etiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D006130:Growth Disorders / Q000209:etiology; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D010587:Phagocytosis; D010641:Phenotype; D016897:Respiratory Burst; D013601:T-Lymphocytes / Q000166:cytology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016335:Zinc Fingers / Q000235:genetics / Q000502:physiology
D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D014157:Transcription Factors