p53 Regulates Hematopoietic Stem Cell Quiescence
Open accessAbstract
The importance of the p53 protein in the cellular response to DNA damage is well known, but its function during steady-state hematopoiesis has not been established. We have defined a critical role of p53 in regulating hematopoietic stem cell quiescence, especially in promoting the enhanced quiescence seen in HSCs that lack the MEF/ELF4 transcription factor. Transcription profiling of HSCs isolated from wild-type and p53 null mice identified Gfi-1 and Necdin as p53 target genes, and using lentiviral vectors to upregulate or knockdown the expression of these genes, we show their importance in regulating HSC quiescence. Establishing the role of p53 (and its target genes) in controlling the cell-cycle entry of HSCs may lead to therapeutic strategies capable of eliminating quiescent cancer (stem) cells.
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USP7 substrates p53 and PTEN regulate stem cell quiescence.
“USP7 substrates (e.g. p53 8, PTEN 9) regulate stem cell quiescence”
From USP7 sustains hematopoietic stem cell homeostasis partially via PU.1 stabilization (2026) · cites this paper as [8]
p53 mediates HSC quiescence independently of p21.
“The mechanism by which p53 mediates HSC quiescence is independent of the CDK inhibitor p21”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [64]
p53 has an important role in regulating stem cell quiescence.
“p53, a master regulator of diverse cellular processes, especially those involved in the maintenance of genomic integrity, has an important role in regulating stem cell quiescence64.”
From Molecular regulation of stem cell quiescence (2013) · cites this paper as [64]
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“This gap is striking, as USP7 substrates (e.g. p53 [8], PTEN [9]) regulate stem cell quiescence, which suggests broader roles in HSC integrity.”
- Authors
- Liu, Y., Elf, S. E., Miyata, Y., Sashida, G., Liu, Y., Huang, G., Di Giandomenico, S., Lee, J. M., Deblasio, A., Menendez, S., Antipin, J., Reva, B., Koff, A., & Nimer, S. D.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Nimer, Stephen D.
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 4
- Issue
- 1
- Pages
- 37-48
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC2839936
- OpenAlex
- W2004838336
- Cited by
- 547
- References
- 57
- Citations by year
- 2026: 14 · 2025: 11 · 2024: 17 · 2023: 28 · 2022: 29 · 2021: 37 · 2020: 29 · 2019: 38 · 2018: 30 · 2017: 26 · 2016: 28 · 2015: 35 · 2014: 25 · 2013: 39 · 2012: 48
- FWCI
- 35.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Memorial Sloan-Kettering Cancer Center
- National Institutes of Health
- National Cancer Institute (P30CA008748)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK52208, R01DK052208, R56DK052208)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- p53, hematopoietic stem cells, stem cell quiescence, GFI1, NDN, p53 target genes, cell cycle entry, steady-state hematopoiesis, cancer stem cells, gene expression profiling
- MeSH terms
- Animals, Cell Cycle, DNA-Binding Proteins, Female, Hematopoiesis, Hematopoietic Stem Cells, Male, Mice, Inbred C57BL, Nerve Tissue Proteins, Nuclear Proteins, Transcription Factors, Transcription, Genetic, Tumor Suppressor Protein p53, Mice, Knockout, Cell Proliferation, Cyclin-Dependent Kinase Inhibitor p21, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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