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PU.1 is not essential for early myeloid gene expression but is required for terminal myeloid differentiation
Open accessAbstract
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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“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].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [21]
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Self-citationFisher, R. C., Olson, M. C., Pongubala, J. M. R., Perkel, J. M., Atchison, M. L., Scott, E. W., & Simon, M. C. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.7.4347 · Cited by 49
Self-citationSpi‐B can functionally replace PU.1 in myeloid but not lymphoid development
Dahl, R. E., Ramírez‐Bergeron, D. L., Rao, S., & Simon, M. C. (2002) · The EMBO Journal · doi:10.1093/emboj/21.9.2220 · Cited by 48
Self-citationZhang, C., Gadue, P. J., Scott, E. W., Atchison, M. L., & Poncz, M. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.42.26236 · Cited by 46
Self-citationKiani, A., Habermann, I., Haase, M., Feldmann, S., Boxberger, S., Sanchez-Fernandez, M. A., Thiede, C., Bornhäuser, M., & Ehninger, G. (2004) · Journal of Leukocyte Biology · doi:10.1189/jlb.0404259 · Cited by 49
Transcriptional mechanisms regulating myeloid-specific genes
Skalnik, D. G. (2002) · Gene · doi:10.1016/s0378-1119(02)00387-6 · Cited by 48
Olweus, J., Thompson, P., & Lund-Johansen, F. (1996) · Blood · doi:10.1182/blood.v88.10.3741.bloodjournal88103741 · Cited by 47
Origin and Emergence of Microglia in the CNS—An Interesting (Hi)story of an Eccentric Cell
Dermitzakis, I., Μanthou, M. E., Meditskou, S., Tremblay, M., Petratos, S., Zoupi, L., Boziki, M. K., Kesidou, E., Simeonidou, C., & Theotokis, P. (2023) · Current Issues in Molecular Biology · doi:10.3390/cimb45030171 · Cited by 55
Metadata
- 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
- bronze
- doi.org
- Licence
- 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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