Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation

Hanno Hock; Melanie J. Hamblen; Heather M. Rooke; David Traver; Roderick T. Bronson; Scott Cameron; Stuart H. Orkin

doi:10.1016/S1074-7613(02)00501-0

Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation

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

Research output: Contribution to journal › Article › peer-review

330 Scopus citations

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.

Original language	English
Pages (from-to)	109-120
Number of pages	12
Journal	Immunity
Volume	18
Issue number	1
DOIs	https://doi.org/10.1016/S1074-7613(02)00501-0
State	Published - 1 Jan 2003
Externally published	Yes

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title = "Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation",

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.",

author = "Hanno Hock and Hamblen, \{Melanie J.\} and Rooke, \{Heather M.\} and David Traver and Bronson, \{Roderick T.\} and Scott Cameron and Orkin, \{Stuart H.\}",

note = "Funding Information: We thank Dan Tenen, Dong-Er Zhang, and Julie Lekstrom-Himes for myeloid gene probes; Richard Mulligan for the MMP retroviral vector; and Anton Berns for genomic maps and clones of Gfi-1. We thank Mark Fleming and Ann Dvorak for review of pathology and ultrastructure. We appreciate the expert assistance of Howard Mulhern, Maris Handley, Herb Levine, Carol Browne, Yuko Fujiwara, Aimee Williams, and Shelly Galusha. We thank Tom Gridley for CJ7 ES cells. H.H. was supported by a Special Fellowship of the Leukemia and Lymphoma Society. S.H.O. is an Investigator of the Howard Hughes Medical Institute. This work was supported in part by a Center of Excellence grant in Molecular Hematology from the NIH.",

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doi = "10.1016/S1074-7613(02)00501-0",

language = "English",

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AU - Hock, Hanno

AU - Hamblen, Melanie J.

AU - Rooke, Heather M.

AU - Traver, David

AU - Bronson, Roderick T.

AU - Cameron, Scott

AU - Orkin, Stuart H.

N1 - Funding Information: We thank Dan Tenen, Dong-Er Zhang, and Julie Lekstrom-Himes for myeloid gene probes; Richard Mulligan for the MMP retroviral vector; and Anton Berns for genomic maps and clones of Gfi-1. We thank Mark Fleming and Ann Dvorak for review of pathology and ultrastructure. We appreciate the expert assistance of Howard Mulhern, Maris Handley, Herb Levine, Carol Browne, Yuko Fujiwara, Aimee Williams, and Shelly Galusha. We thank Tom Gridley for CJ7 ES cells. H.H. was supported by a Special Fellowship of the Leukemia and Lymphoma Society. S.H.O. is an Investigator of the Howard Hughes Medical Institute. This work was supported in part by a Center of Excellence grant in Molecular Hematology from the NIH.

PY - 2003/1/1

Y1 - 2003/1/1

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/0037244284

U2 - 10.1016/S1074-7613(02)00501-0

DO - 10.1016/S1074-7613(02)00501-0

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SN - 1074-7613

VL - 18

SP - 109

EP - 120

JO - Immunity

JF - Immunity

IS - 1

ER -

Intrinsic requirement for zinc finger transcription factor Gfi-1 in neutrophil differentiation

Abstract

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