p53 pathway is involved in cell competition during mouse embryogenesis
Open accessAbstract
Significance: In response to a variety of stress signals, tumor suppressor p53 is activated to influence the cellular outcome. Various stresses result in different levels of p53 activation. We demonstrate here that during mouse development, uniform activation of p53 at a moderate level is well tolerated in the embryos. In contrast, mild activation of p53 in individual cells leads to a growth disadvantage and their out-competition when they are present together with nonactivated cells. These results suggest that p53 may coordinate at a multicellular level for optimal stress response and fitness of the organism.
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The chronic elimination of pu.1-deficient microglia in zebrafish is mediated by Tp53-dependent cell competition.
“we further showed that the chronic elimination of pu.1 -deficent microglia in zebrafish is mediated by Tp53-dependent cell competition”
From Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals (2023) · cites this paper as Zhang et al., 2017
The Results report p53-dependent out-competition of Mdm2+/−Mdm4+/− cells in mosaic mouse embryos. The paper does not study pu.1-deficient microglia, zebrafish, or their chronic elimination, so it supports the general mechanism but not the specific claim. (LLM, conf=0.88)
Experimental — accuracy not yet measuredTp53 is involved in cell competition regulation in both hematopoietic and non-hemopoietic tissues.
“Tp53 is also involved in cell competition regulation in both hematopoietic and non-hemopoietic tissues (Bondar & Medzhitov, 2010, Zhang, Xie et al., 2017).”
From Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals (2023) · cites this paper as Zhang, Xie et al., 2017
Tp53-dependent cell competition depends on the relative level of Tp53 in competing cells.
“which has been shown to depend on the relative level of Tp53 in competing cells (Bondar & Medzhitov, 2010, Zhang et al., 2017).”
From Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals (2023) · cites this paper as Zhang et al., 2017
Tp53 is involved in cell competition regulation in both hematopoietic and non-hemopoietic tissues.
“Tp53 is also involved in cell competition regulation in both hematopoietic and non-hemopoietic tissues (Bondar and Medzhitov, 2010; Zhang et al., 2017).”
From Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals (2025) · cites this paper as Zhang et al., 2017
Tp53-dependent cell competition depends on the relative level of Tp53 in competing cells.
“which has been shown to depend on the relative level of Tp53 in competing cells (Bondar and Medzhitov, 2010; Zhang et al., 2017).”
From Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals (2025) · cites this paper as Zhang et al., 2017
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Valverde-Lopez, J. A., Li-Bao, L., Díaz-Díaz, C., Sierra, R., Santos, E., Giovinazzo, G., & Torres, M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.21.541667 · Cited by 4 · see citing works
Cell competition as an emerging mechanism and therapeutic target in cancer
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Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammals
Wu, Y., Guo, W., Kuang, H., Wu, X., Trinh, T. H., Wang, Y., Zhao, S., Wen, Z., & Yu, T. (2023) · bioRxiv (Preprint) · doi:10.1101/2023.12.14.570333 · Cited by 1 · see citing works
“Collectively, these results indicate that the dosage-dependent cell competition-mediated regulation of microglia maintenance by SPI1/PU.1 is evolutionarily conserved from teleost to mammals.”
Rlip Depletion Alters Oncogene Transcription at Multiple Distinct Regulatory Levels
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Developmental tolerance and disease implications of aneuploidy
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Competitive signaling and cellular communications in myocardial infarction response
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Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammalsPreprint
Wu, Y., Guo, W., Kuang, H., Wu, X., Wang, Y., Zhao, S., Wen, Z., & Yu, T. (2025) · eLife · doi:10.7554/elife.105788.1
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Pu.1/Spi1 dosage controls the turnover and maintenance of microglia in zebrafish and mammalsPreprint
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Wounding induces preexisting multinucleated cells to survive and thrive as leader cellsPreprint
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Cell competition in tumorigenesis and epithelial defence against cancer
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Critical role of cell competition in gliomagenesisPreprint
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Self-citation
- Authors
- Zhang, G., Xie, Y., Zhou, Y., Xiang, C., Chen, L., Zhang, C., Hou, X., Chen, J., Zong, H., & Liu, G.
- Affiliations
- Model Animal Research Center (CN)
- Jiangxi University of Traditional Chinese Medicine (CN)
- University of Virginia (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2017-01-03
- Volume
- 114
- Issue
- 3
- Pages
- 498-503
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC5255589
- OpenAlex
- W2564767099
- Cited by
- 69
- References
- 41
- Citations by year
- 2026: 3 · 2025: 14 · 2024: 4 · 2023: 7 · 2022: 7 · 2021: 5 · 2020: 8 · 2019: 9 · 2018: 10 · 2017: 2
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31171305, 31571406)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Keywords
- p53, cell competition, mouse embryo development, genetic mosaicism, cell fitness, cell fate, tumor suppressor function
- MeSH terms
- Animals, Female, Male, Mice, Inbred C57BL, Mosaicism, Pancreas, Phenotype, Pregnancy, Proto-Oncogene Proteins, Signal Transduction, Tumor Suppressor Protein p53, Apoptosis, Mice, Knockout, Embryonic Development, Cell Proliferation, Mice, Proto-Oncogene Proteins c-mdm2, Haploinsufficiency, Cell Cycle Checkpoints
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