p53 Regulates Hematopoietic Stem Cell Quiescence

Yan Liu, Shannon E. Elf, Yasuhiko Miyata, Goro Sashida, Yuhui Liu, Gang Huang, Silvana Di Giandomenico, Jennifer M. Lee, Anthony Deblasio, Silvia Menendez, Jack Antipin, Boris Reva, Andrew Koff, Stephen D. Nimer

Research output: Contribution to journalArticle

343 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)37-48
Number of pages12
JournalCell Stem Cell
Volume4
Issue number1
DOIs
StatePublished - Jan 9 2009
Externally publishedYes

Keywords

  • CELLCYCLE
  • STEMCELL

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

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  • Cite this

    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. (2009). p53 Regulates Hematopoietic Stem Cell Quiescence. Cell Stem Cell, 4(1), 37-48. https://doi.org/10.1016/j.stem.2008.11.006