p53 Regulates Hematopoietic Stem Cell Quiescence

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 quiescenc...

Full description

Saved in:
Bibliographic Details
Published in:Cell stem cell 2009-01, Vol.4 (1), p.37-48
Main Authors: YAN LIU, ELF, Shannon E, ANTIPIN, Jack, REVA, Boris, KOFF, Andrew, NIMER, Stephen D, MIYATA, Yasuhiko, SASHIDA, Goro, YUHUI LIU, GANG HUANG, DI GIANDOMENICO, Silvana, LEE, Jennifer M, DEBLASIO, Anthony, MENENDEZ, Silvia
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cell Cycle
Cell physiology
Cell Proliferation
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Cyclin-Dependent Kinase Inhibitor p21 - metabolism
DNA-Binding Proteins - deficiency
DNA-Binding Proteins - metabolism
Female
Fundamental and applied biological sciences. Psychology
Hematopoiesis
Hematopoietic Stem Cells - cytology
Hematopoietic Stem Cells - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Molecular and cellular biology
Nerve Tissue Proteins - metabolism
Nuclear Proteins - metabolism
Transcription Factors - deficiency
Transcription Factors - metabolism
Transcription, Genetic
Tumor Suppressor Protein p53 - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1934-5909
1875-9777
DOI:10.1016/j.stem.2008.11.006