ICSBP Directs Bipotential Myeloid Progenitor Cells to Differentiate into Mature Macrophages

Tamura, Tomohiko; Nagamura-Inoue, Tokiko; Shmeltzer, Zeevik; Kuwata, Takeshi; Ozato, Keiko

doi:10.1016/s1074-7613(00)00016-9

Cited by 305Hematopoietic Stem Cell TransplantationImmune cells in cancerGenomics and Chromatin Dynamics

ICSBP Directs Bipotential Myeloid Progenitor Cells to Differentiate into Mature Macrophages

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Tamura, Tomohiko, Nagamura-Inoue, Tokiko, Shmeltzer, Zeevik, Kuwata, Takeshi, Ozato, Keiko·2000·Immunity

DOI 10.1016/s1074-7613(00)00016-9

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Abstract

During hematopoiesis, myeloid progenitor cells give rise to granulocytes and macrophages. To study the role for ICSBP, a hematopoietic cell-specific transcription factor in myeloid cell development, the gene was introduced into myeloid progenitor cells established from ICSBP-/- mice. ICSBP retrovirus-transduced cells differentiated into mature macrophages with phagocytic activity, which coincided with the induction of specific target DNA binding activity. Similar to macrophages in vivo, ICSBP-transduced cells were growth arrested, expressed many macrophage-specific genes, and responded to macrophage activation signals. Contrary to this, ICSBP transducion led to repression of granulocyte-specific genes and inhibited G-CSF-mediated granulocytic differentiation in these and other myeloid progenitor cells. Together, ICSBP has a key role in the myeloid cell lineage selection and macrophage maturation.

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ICSBP-/- mice harbor an increased number of myeloid progenitor cells, and the -/- progenitors preferentially give rise to granulocytes, although they cannot efficiently generate macrophages.
“ICSBP 2 / 2 mice harbor an increased number of myeloid progenitor cells, and the 2 / 2 progenitors preferentially give rise to granulocytes, although they cannot efficiently generate another descendant of the myeloid lineage, macrophages.”
From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [54]
Studies with myeloid progenitor cells have shown that ICSBP drives their differentiation toward macrophage, whereas it inhibits granulocyte differentiation.
“Studies with myeloid progenitor cells have shown that ICSBP drives their differentiation toward macrophage, whereas it inhibits granulocyte differentiation.”
From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [54]
ICSBP-/- myeloid progenitor cell lines grow in a GM-CSF-dependent manner and differentiate into mature granulocytes in response to G-CSF; transduction of ICSBP causes marked differentiation into mature macrophages with phagocytic activity, represses granulocyte-specific genes, and inhibits G-CSF-mediated granulocyte growth and differentiation.
“These progenitor cells grew in a GM-CSF-dependent manner and were capable of differentiating into mature granulocytes in response to G-CSF.”
From Review: ICSBP/IRF-8: Its Regulatory Roles in the Development of Myeloid Cells (2002) · cites this paper as [54]
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.”
From Single-cell analysis of mixed-lineage states leading to a binary cell fate choice (2016) · cites this paper as [10]

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Authors: Tamura, T., Nagamura-Inoue, T., Shmeltzer, Z., Kuwata, T., & Ozato, K.
Affiliations: National Institutes of Health (US)
Corresponding author: Ozato, Keiko
ORCID: Tamura, Tomohiko
Kuwata, Takeshi
Venue: Immunity
Publisher: Elsevier BV
Published: 2000-08
Volume: 13
Issue: 2
Pages: 155-165
ISSN: 1074-7613 (ISSN-L)
DOI: 10.1016/s1074-7613(00)00016-9
OpenAlex: W2045510187
Semantic Scholar: e76d10279936b3a33a90ea0b41da0d905924ac8d
Cited by: 305
References: 54
Citations by year: 2026: 4 · 2025: 6 · 2024: 11 · 2023: 5 · 2022: 8 · 2021: 10 · 2020: 14 · 2019: 10 · 2018: 6 · 2017: 15 · 2016: 15 · 2015: 11 · 2014: 18 · 2013: 19 · 2012: 13
FWCI: 8.55
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 4733 d)
Locations: Immunity (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords: IRF8, macrophage differentiation, myeloid progenitor cells, hematopoiesis, lineage selection, transcription factors, granulocytic differentiation, granulocyte colony-stimulating factor, phagocytosis, macrophage activation, retroviral transduction, gene targeting
MeSH terms: Interferon Regulatory Factor-8, Animals, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Hematopoietic Stem Cells, Interferons, Macrophages, Repressor Proteins, Leukopoiesis, Interferon Regulatory Factors, Mice

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ICSBP Directs Bipotential Myeloid Progenitor Cells to Differentiate into Mature Macrophages

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