Cited by 191Hematopoietic Stem Cell TransplantationGenomics and Chromatin DynamicsDevelopmental Biology and Gene Regulation

PU.1 is not essential for early myeloid gene expression but is required for terminal myeloid differentiation

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Olson, Marilyn C., Scott, Edward W., Hack, Andrew A., Su, Gloria H., Tenen, Daniel G., Singh, Harinder, Simon, M.Celeste·1995·Immunity

Abstract

We have previously shown using gene targeting that PU.1 is essential for the development of lymphoid and myeloid lineages during fetal liver hematopoiesis. We now show that PU.1 is required for the maturation of yolk sac-derived myeloid progenitors and for the differentiation of ES cells into macrophages. The role of PU.1 in regulating target genes, thought to be critical in the development of monocytes and granulocytes, has been analyzed. Early genes such as GM-CSFR, G-CSFR, and myeloperoxidase are expressed in PU.1-/- embryos and differentiated PU.1-/- ES cells. However, the expression of genes associated with terminal myeloid differentiation (CD11b, CD64, and M-CSFR) is eliminated in differentiated PU.1-/- ES cells. Development of macrophages is restored with the introduction of a PU.1 cDNA regulated by its own promoter. The PU.1-/- ES cells represent an important model for analyzing myeloid cell development.

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Crossref · 10.1016/1074-7613(95)90060-8

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  • All activated macrophages express high levels of RUNX1 and PU.1, thought to be global regulators of macrophage phenotypic expression.

    “All activated macrophages, regardless of polarization state, express high levels of the transcription factors runt-related transcription factor 1 (RUNX1) and PU.1, which are thought to represent global regulators of macrophage phenotypic expression [20–22].”

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Authors
Olson, M. C., Scott, E. W., Hack, A. A., Su, G. H., Tenen, D. G., Singh, H., & Simon, M. C.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Beth Israel Deaconess Medical Center (US)
Venue
Immunity
Publisher
Elsevier BV
Published
1995-12
Volume
3
Issue
6
Pages
703-714
ISSN
1074-7613 (ISSN-L)
OpenAlex
W2050347737
Cited by
191
References
58
Citations by year
2025: 3 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 2 · 2020: 3 · 2018: 1 · 2017: 8 · 2016: 4 · 2015: 2 · 2014: 7 · 2013: 3 · 2012: 4
FWCI
9.53
Type
journal article
Language
en
Open access
Locations
  • Immunity (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health (2r01hl052094-05a1, 5f32ai008933-02)
  • National Heart, Lung, and Blood Institute (HL5-2094)
  • National Institute of Allergy and Infectious Diseases (F32 AI08933)
Topics
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
PU.1, myeloid differentiation, embryonic stem cells, macrophage differentiation, GM-CSF receptor, G-CSF receptor, myeloperoxidase, CD11b, CD64, M-CSF receptor, hematopoiesis, monocytes, granulocytes, transcription factors
MeSH terms
Proto-Oncogene Protein Spi-1, Animals, Base Sequence, Cell Differentiation, Cells, Cultured, Female, Granulocytes, Hematopoietic Stem Cells, Male, Mice, Mutant Strains, Molecular Sequence Data, Monocytes, Proto-Oncogene Proteins, Trans-Activators, Gene Expression Regulation, Developmental, Mice

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