Authors: | Liu, Y.; Elf, S. E.; Miyata, Y.; Sashida, G.; Huang, G.; Di Giandomenico, S.; Lee, J. M.; Deblasio, A.; Menendez, S.; Antipin, J.; Reva, B.; Koff, A.; Nimer, S. D. |
Article Title: | p53 Regulates Hematopoietic Stem Cell Quiescence |
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. © 2009 Elsevier Inc. All rights reserved. |
Keywords: | controlled study; dna-binding proteins; nonhuman; protein function; cell proliferation; animal cell; mouse; animals; mice; mice, knockout; mus; cell cycle; animal experiment; nerve tissue proteins; genetic transcription; transcription, genetic; wild type; protein p53; mice, inbred c57bl; transcription factors; nuclear proteins; gene expression regulation; stemcell; cancer stem cell; cell isolation; lentivirus vector; hematopoietic stem cells; tumor suppressor protein p53; hematopoiesis; cellcycle; upregulation; hematopoietic stem cell; cyclin-dependent kinase inhibitor p21; bone marrow transplantation; cell cycle regulation; necdin |
Journal Title: | Cell Stem Cell |
Volume: | 4 |
Issue: | 1 |
ISSN: | 1934-5909 |
Publisher: | Cell Press |
Date Published: | 2009-01-09 |
Start Page: | 37 |
End Page: | 48 |
Language: | English |
DOI: | 10.1016/j.stem.2008.11.006 |
PUBMED: | 19128791 |
PROVIDER: | scopus |
PMCID: | PMC2839936 |
DOI/URL: | |
Notes: | --- - "Cited By (since 1996): 49" - "Export Date: 30 November 2010" - "Source: Scopus" |