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

319 Citations (Scopus)

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

Fingerprint

Gene Knockdown Techniques
Neoplastic Stem Cells
p53 Genes
Hematopoiesis
Hematopoietic Stem Cells
DNA Damage
Cell Cycle
Transcription Factors
Up-Regulation
Gene Expression
Genes
Proteins
Therapeutics
necdin

Keywords

  • CELLCYCLE
  • STEMCELL

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine
  • Genetics

Cite this

Liu, Y., Elf, S. E., Miyata, Y., Sashida, G., Liu, Y., Huang, G., ... 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

p53 Regulates Hematopoietic Stem Cell Quiescence. / Liu, Yan; Elf, Shannon E.; Miyata, Yasuhiko; Sashida, Goro; Liu, Yuhui; Huang, Gang; Di Giandomenico, Silvana; Lee, Jennifer M.; Deblasio, Anthony; Menendez, Silvia; Antipin, Jack; Reva, Boris; Koff, Andrew; Nimer, Stephen D.

In: Cell Stem Cell, Vol. 4, No. 1, 09.01.2009, p. 37-48.

Research output: Contribution to journalArticle

Liu, Y, Elf, SE, Miyata, Y, Sashida, G, Liu, Y, Huang, G, Di Giandomenico, S, Lee, JM, Deblasio, A, Menendez, S, Antipin, J, Reva, B, Koff, A & Nimer, SD 2009, 'p53 Regulates Hematopoietic Stem Cell Quiescence', Cell Stem Cell, vol. 4, no. 1, pp. 37-48. https://doi.org/10.1016/j.stem.2008.11.006
Liu Y, Elf SE, Miyata Y, Sashida G, Liu Y, Huang G et al. p53 Regulates Hematopoietic Stem Cell Quiescence. Cell Stem Cell. 2009 Jan 9;4(1):37-48. https://doi.org/10.1016/j.stem.2008.11.006
Liu, Yan ; Elf, Shannon E. ; Miyata, Yasuhiko ; Sashida, Goro ; Liu, Yuhui ; Huang, Gang ; Di Giandomenico, Silvana ; Lee, Jennifer M. ; Deblasio, Anthony ; Menendez, Silvia ; Antipin, Jack ; Reva, Boris ; Koff, Andrew ; Nimer, Stephen D. / p53 Regulates Hematopoietic Stem Cell Quiescence. In: Cell Stem Cell. 2009 ; Vol. 4, No. 1. pp. 37-48.
@article{471a90e0d83f427eba4e161079788820,
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.",
keywords = "CELLCYCLE, STEMCELL",
author = "Yan Liu and Elf, {Shannon E.} and Yasuhiko Miyata and Goro Sashida and Yuhui Liu and Gang Huang and {Di Giandomenico}, Silvana and Lee, {Jennifer M.} and Anthony Deblasio and Silvia Menendez and Jack Antipin and Boris Reva and Andrew Koff and Nimer, {Stephen D.}",
year = "2009",
month = "1",
day = "9",
doi = "10.1016/j.stem.2008.11.006",
language = "English (US)",
volume = "4",
pages = "37--48",
journal = "Cell Stem Cell",
issn = "1934-5909",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - p53 Regulates Hematopoietic Stem Cell Quiescence

AU - Liu, Yan

AU - Elf, Shannon E.

AU - Miyata, Yasuhiko

AU - Sashida, Goro

AU - Liu, Yuhui

AU - Huang, Gang

AU - Di Giandomenico, Silvana

AU - Lee, Jennifer M.

AU - Deblasio, Anthony

AU - Menendez, Silvia

AU - Antipin, Jack

AU - Reva, Boris

AU - Koff, Andrew

AU - Nimer, Stephen D.

PY - 2009/1/9

Y1 - 2009/1/9

N2 - 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.

AB - 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.

KW - CELLCYCLE

KW - STEMCELL

UR - http://www.scopus.com/inward/record.url?scp=58049216794&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58049216794&partnerID=8YFLogxK

U2 - 10.1016/j.stem.2008.11.006

DO - 10.1016/j.stem.2008.11.006

M3 - Article

VL - 4

SP - 37

EP - 48

JO - Cell Stem Cell

JF - Cell Stem Cell

SN - 1934-5909

IS - 1

ER -