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 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.
Liu
Yan
Y
Molecular Phamacology and Chemistry Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Elf
Shannon E
SE
Miyata
Yasuhiko
Y
Sashida
Goro
G
Liu
Yuhui
Y
Huang
Gang
G
Di Giandomenico
Silvana
S
Lee
Jennifer M
JM
Deblasio
Anthony
A
Menendez
Silvia
S
Antipin
Jack
J
Reva
Boris
B
Koff
Andrew
A
Nimer
Stephen D
SD
D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000378:metabolism; D005260:Female; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C491779:Elf4 protein, mouse; C079873:Gfi1 protein, mouse; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C069766:necdin