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The Transcription Factor PU.1 Controls Dendritic Cell Development and Flt3 Cytokine Receptor Expression in a Dose-Dependent Manner
Open accessAbstract
The transcription factor PU.1 plays multiple context and concentration dependent roles in lymphoid and myeloid cell development. Here we showed that PU.1 (encoded by Sfpi1) was essential for dendritic cell (DC) development in vivo and that conditional ablation of PU.1 in defined precursors, including the common DC progenitor, blocked Flt3 ligand-induced DC generation in vitro. PU.1 was also required for the parallel granulocyte-macrophage colony stimulating factor-induced DC pathway from early hematopoietic progenitors. Molecular studies demonstrated that PU.1 directly regulated Flt3 in a concentration-dependent manner, as Sfpi1(+/-) cells displayed reduced expression of Flt3 and impaired DC formation. These studies identify PU.1 as a critical regulator of both conventional and plasmacytoid DC development and provide one mechanism how altered PU.1 concentration can have profound functional consequences for hematopoietic cell development.
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“PU.1 is directly required to maintain the expression of the cytokine receptor Flt3 that is indispensable for progenitors with B and T cell potentials (73).”
From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [73]
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Metadata
- Authors
- Carotta, S., Dakic, A., D'Amico, A., Pang, S. H. M., Greig, K. T., Nutt, S. L., & Wu, L.
- Affiliations
- Walter and Eliza Hall Institute of Medical Research (AU)
- The University of Melbourne (AU)
- Corresponding author
- Nutt, Stephen L.
- Wu, Li
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2010-05
- Volume
- 32
- Issue
- 5
- Pages
- 628-641
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W1963617750
- Cited by
- 279
- References
- 53
- Citations by year
- 2026: 12 · 2025: 4 · 2024: 14 · 2023: 8 · 2022: 10 · 2021: 13 · 2020: 19 · 2019: 15 · 2018: 16 · 2017: 18 · 2016: 15 · 2015: 23 · 2014: 22 · 2013: 29 · 2012: 27
- FWCI
- 12.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1209 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Leukaemia Foundation
- University of Melbourne
- Australian Research Council
- National Health and Medical Research Council
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- PU.1, dendritic cell development, FLT3, Flt3 ligand, plasmacytoid dendritic cells, myeloid dendritic cells, GM-CSF, transcriptional regulation, dose-dependent gene expression, conditional gene deletion, hematopoietic progenitor cells
- MeSH terms
- Proto-Oncogene Protein Spi-1, Animals, Base Sequence, Cell Differentiation, Cells, Cultured, Dendritic Cells, Dose-Response Relationship, Drug, Flow Cytometry, Membrane Proteins, Mice, Transgenic, Molecular Sequence Data, Promoter Regions, Genetic, Proto-Oncogene Proteins, Trans-Activators, Polymerase Chain Reaction, Models, Immunological, Mice
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