Necdin, a p53 target gene, regulates the quiescence and response to genotoxic stress of hematopoietic stem/progenitor cells

Takashi Asai, Yan Liu, Silvana Di Giandomenico, Narae Bae, Delphine Ndiaye-Lobry, Anthony Deblasio, Silvia Menendez, Yevgeniy Antipin, Boris Reva, Rachel Wevrick, Stephen D. Nimer

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

We recently defined a critical role for p53 in regulating the quiescence of adult hematopoietic stem cells (HSCs) and identified necdin as a candidate p53 target gene. Necdin is a growth-suppressing protein and the gene encoding it is one of several that are deleted in patients with Prader-Willi syndrome. To define the intrinsic role of necdin in adult hematopoiesis, in the present study, we transplanted necdin-null fetal liver cells into lethally irradiated recipients. We show that necdin-null adult HSCs are less quiescent and more proliferative than normal HSCs, demonstrating the similar role of necdin and p53 in promoting HSC quiescence during steady-state conditions. However, wild-type recipients repopulated with necdin-null hematopoietic stem/progenitor cells show enhanced sensitivity to irradiation and chemotherapy, with increased p53-dependent apoptosis, myelosuppression, and mortality. Necdin controls the HSC response to genotoxic stress via both cell-cycle-dependent and cell-cycle-independent mechanisms, with the latter occurring in a Gas2L3-dependent manner.We conclude that necdin functions as a molecular switch in adult hematopoiesis, acting in a p53-like manner to promote HSC quiescence in the steady state, but suppressing p53-dependent apoptosis in response to genotoxic stress.

Original languageEnglish
Pages (from-to)1601-1612
Number of pages12
JournalBlood
Volume120
Issue number8
DOIs
StatePublished - Aug 23 2012

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p53 Genes
Hematopoietic Stem Cells
Stem cells
DNA Damage
Genes
Adult Stem Cells
Hematopoiesis
Cell Cycle
Cells
Apoptosis
Prader-Willi Syndrome
necdin
Gene encoding
Chemotherapy
Liver
Switches
Irradiation
Drug Therapy
Mortality
Growth

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Necdin, a p53 target gene, regulates the quiescence and response to genotoxic stress of hematopoietic stem/progenitor cells. / Asai, Takashi; Liu, Yan; Di Giandomenico, Silvana; Bae, Narae; Ndiaye-Lobry, Delphine; Deblasio, Anthony; Menendez, Silvia; Antipin, Yevgeniy; Reva, Boris; Wevrick, Rachel; Nimer, Stephen D.

In: Blood, Vol. 120, No. 8, 23.08.2012, p. 1601-1612.

Research output: Contribution to journalArticle

Asai, T, Liu, Y, Di Giandomenico, S, Bae, N, Ndiaye-Lobry, D, Deblasio, A, Menendez, S, Antipin, Y, Reva, B, Wevrick, R & Nimer, SD 2012, 'Necdin, a p53 target gene, regulates the quiescence and response to genotoxic stress of hematopoietic stem/progenitor cells', Blood, vol. 120, no. 8, pp. 1601-1612. https://doi.org/10.1182/blood-2011-11-393983
Asai, Takashi ; Liu, Yan ; Di Giandomenico, Silvana ; Bae, Narae ; Ndiaye-Lobry, Delphine ; Deblasio, Anthony ; Menendez, Silvia ; Antipin, Yevgeniy ; Reva, Boris ; Wevrick, Rachel ; Nimer, Stephen D. / Necdin, a p53 target gene, regulates the quiescence and response to genotoxic stress of hematopoietic stem/progenitor cells. In: Blood. 2012 ; Vol. 120, No. 8. pp. 1601-1612.
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AU - Ndiaye-Lobry, Delphine

AU - Deblasio, Anthony

AU - Menendez, Silvia

AU - Antipin, Yevgeniy

AU - Reva, Boris

AU - Wevrick, Rachel

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