Abstract
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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Cycle*
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Cell Proliferation
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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DNA-Binding Proteins / deficiency
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DNA-Binding Proteins / metabolism
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Female
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Hematopoiesis
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Hematopoietic Stem Cells / cytology*
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Hematopoietic Stem Cells / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Nerve Tissue Proteins / metabolism
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Nuclear Proteins / metabolism
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Transcription Factors / deficiency
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Transcription Factors / metabolism
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Transcription, Genetic
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Tumor Suppressor Protein p53 / metabolism*
Substances
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Cyclin-Dependent Kinase Inhibitor p21
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DNA-Binding Proteins
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Elf4 protein, mouse
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Gfi1 protein, mouse
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Nerve Tissue Proteins
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Nuclear Proteins
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Transcription Factors
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Tumor Suppressor Protein p53
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necdin