NPR-C protects embryonic stem cells from apoptosis by regulating p53 levels

Essam M. Abdelalim, Ikuo Tooyama

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The identification of intrinsic factors required for propagation of self-renewing embryonic stem (ES) cells is important to improve the efficiency of expansion of ES cells for therapeutic purposes. Here, we report a novel role for natriuretic peptide receptor-C (NPR-C) in the survival of murine ES cells. We found that NPR-C was highly expressed in ES cells and was downregulated during ES cell differentiation. Knockdown of NPR-C in ES cells by using a small-interfering RNA resulted in apoptotic cell death, and the induction of p53 protein expression. Conversely, chemical inhibition of p53 by α-pifithrin significantly reduced apoptosis in NPR-C-deficient cells. cANF (4-23), a selective NPR-C agonist, protected ES cells against oxidative stress-induced apoptosis, and blocked activation of p53 and Nanog suppression in the presence of DNA-damaging agents. Thus, NPR-C is required to control DNA damage-induced p53 levels to maintain ES cell self-renewal.

Original languageEnglish
Pages (from-to)1264-1271
Number of pages8
JournalStem Cells and Development
Volume21
Issue number8
DOIs
Publication statusPublished - 20 May 2012

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ASJC Scopus subject areas

  • Hematology
  • Developmental Biology
  • Cell Biology

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