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PU.1 induces myeloid lineage commitment in multipotent hematopoietic progenitors
Open accessAbstract
Little is known about the transcription factors that mediate lineage commitment of multipotent hematopoietic precursors. One candidate is the Ets family transcription factor PU.1, which is expressed in myeloid and B cells and is required for the development of both these lineages. We show here that the factor specifically instructs transformed multipotent hematopoietic progenitors to differentiate along the myeloid lineage. This involves not only the up-regulation of myeloid-specific cell surface antigens and the acquisition of myeloid growth-factor dependence but also the down-regulation of progenitor/thrombocyte-specific cell-surface markers and GATA-1. Both effects require an intact PU.1 transactivation domain. Whereas sustained activation of an inducible form of the factor leads to myeloid lineage commitment, short-term activation leads to the formation of immature eosinophils, indicating the existence of a bilineage intermediate. Our results suggest that PU.1 induces myeloid lineage commitment by the suppression of a master regulator of nonmyeloid genes (such as GATA-1) and the concomitant activation of multiple myeloid genes.
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In the citing paper
“PU.1 regulates lineage-specific gene expression in a dose-dependent manner21–23.”
From Lymphoid gene expression supports neuroprotective microglia function (2025) · cites this paper as [21]
Experimental — accuracy not yet measuredIn the citing paper
“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 [22]
In the citing paper
“Interestingly, C/EBP-α is also known to cooperate with PU.1 in controlling the expression of the GM-CSF receptor [108].”
From PU.1 and partners: regulation of haematopoietic stem cell fate in normal and malignant haematopoiesis (2009) · cites this paper as [108]
In the citing paper
“During lineage commitment, activation of specific transcription factors has been shown to direct precursor cells to a particular differentiation pathway (3, 41).”
From Negative cross-talk between hematopoietic regulators: GATA proteins repress PU.1 (1999) · cites this paper as [41]
In the citing paper
“and C/EBP⑀ in particular) are essential for the commitment and/or terminal differentiation of myeloid progenitors to the eosinophil lineage (1)(2)(3)(4)(5)(6)(7)(8)(9).”
From Novel Combinatorial Interactions of GATA-1, PU.1, and C/EBPε Isoforms Regulate Transcription of the Gene Encoding Eosinophil Granule Major Basic Protein (2002) · cites this paper as [1]
In the citing paper
“PU.1 probably plays an important role at several stages in the differentiation process, and there is evidence that it is active at an early stage, mediating commitment of multipotential progenitor cells to the myeloid lineage.8”
From Granulocyte inducer C/EBPα inactivates the myeloid master regulator PU.1: possible role in lineage commitment decisions (2002) · cites this paper as [8]
In the citing paper
“PU.1 has been demonstrated to instruct transformed chicken multipotent hematopoietic progenitors to differentiate along the myeloid lineage.8”
From Granulocyte inducer C/EBPα inactivates the myeloid master regulator PU.1: possible role in lineage commitment decisions (2002) · cites this paper as [8]
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Citations
Cites
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Self-citationMafB Is an Interaction Partner and Repressor of Ets-1 That Inhibits Erythroid Differentiation
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Self-citationDistinct C/EBP functions are required for eosinophil lineage commitment and maturation
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Self-citationActivation of Transcription by PU.1 Requires both Acidic and Glutamine Domains
Klemsz, M. J., & Maki, R. A. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.1.390 · Cited by 93
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Transcriptional regulation of macrophage polarization: enabling diversity with identity
Lawrence, T., & Natoli, G. (2011) · Nature Reviews Immunology · doi:10.1038/nri3088 · Cited by 2,284
“1, which must be constantly expressed at high levels to induce and then maintain macrophage differentiatio”
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Auffray, C., Sieweke, M. H., & Geissmann, F. (2009) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132557 · Cited by 1,745
“1 can induce myeloid commitment in immature multipotent progenitor cells (30) and is required for the generation of CMP in early myelopoiesis (31, 32).”
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“PU.1 is absolutely required for myeloid lineage commitment (Nerlov and Graf, 1998; Iwasaki et al., 2005).”
Background
Metadata
- Authors
- Nerlov, C., & Graf, T.
- Affiliations
- European Molecular Biology Laboratory (DE)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 1998-08-01
- Volume
- 12
- Issue
- 15
- Pages
- 2403-2412
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC317050
- OpenAlex
- W1974612283
- Cited by
- 449
- References
- 46
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 12 · 2023: 16 · 2022: 7 · 2021: 22 · 2020: 18 · 2019: 19 · 2018: 13 · 2017: 21 · 2016: 16 · 2015: 17 · 2014: 15 · 2013: 27 · 2012: 17
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sundhed og Sygdom, Det Frie Forskningsråd
- Medical Research Council
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Keywords
- PU.1, ETS transcription factors, myeloid lineage commitment, hematopoietic progenitor cells, GATA-1, transactivation domain, eosinophils, cell surface markers
- MeSH terms
- Proto-Oncogene Protein Spi-1, Alleles, Animals, Cell Differentiation, Chick Embryo, DNA-Binding Proteins, Hematopoiesis, Hematopoietic Stem Cells, Humans, Proto-Oncogene Proteins, Transcription Factors, Transformation, Genetic, Trans-Activators, Gene Expression Regulation, Developmental, Erythroid-Specific DNA-Binding Factors, GATA1 Transcription Factor
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