New Proteomic Insights on the Role of NPR-A in Regulating Self-Renewal of Embryonic Stem Cells

Sameh Magdeldin, Tadashi Yamamoto, Ikuo Tooyama, Essam Mohamed

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Embryonic stem cells (ESCs) have the ability to self-renew indefinitely and they can give unlimited source of cells and tissues for cellular therapies. Recently, the natriuretic peptide receptor A (NPR-A) has been recognized as an important regulator for the self-renewal of ESCs. To gain insights into possible novel mechanisms involved in NPR-A pathway that presumably regulates self-renewal and survival of ESCs, we utilized a comprehensive label-free proteomics technology in our study. Targeting of NPR-A gene with small interfering RNA (siRNA) resulted in the inhibition of ESCs self-renewal. Coherently, quantitative label-free shotgun proteomic analysis identified differentially expressed proteins involved in several biological processes, including cell cycle regulation, cell proliferation, cell fate specification, and apoptosis. Interestingly, in addition to Oct4 Nanog, and Sox2, other proteins involved in ESCs self-renewal were down-regulated after NPR-A knockdown, such as heterogeneous nuclear ribonucleoprotein A2/B1 (ROA2), non-POU domain-containing octamer-binding protein (Nono), nucleoplasmin (Npm1), histone H2A type 1-B/E (histone H2A.2), SW1/SNF complex (Brg1), polycomb protein Suz12 (Suz12), and cyclin-dependent kinase 4 (Cdk4). Furthermore, several protein candidates involved in early differentiation and cell death were up-regulated or down-regulated as a result of NPR-A knockdown, including importin subunit alpha-4 (Impα4), importin-5 (Ipo5), H3 histones, core histone macro-H2A.1 (H2A.y), apurine/apyrimidine endonuclease 1 (Apex1), 78-kDa glucose-regulated protein (Grp78), and programmed cell death 5 (Pdcd5). Overall, these findings depict a comprehensive view to our understanding of the pathways involved in the role of NPR-A in maintaining ESC functions.

Original languageEnglish
Pages (from-to)561-572
Number of pages12
JournalStem Cell Reviews and Reports
Volume10
Issue number4
DOIs
Publication statusPublished - 1 Aug 2014

Fingerprint

Embryonic Stem Cells
Proteomics
Histones
Heterogeneous-Nuclear Ribonucleoprotein Group A-B
Nucleoplasmins
Proteins
alpha Karyopherins
DNA-(Apurinic or Apyrimidinic Site) Lyase
Cyclin-Dependent Kinase 4
Karyopherins
Biological Phenomena
Apoptosis Regulatory Proteins
Firearms
Cell- and Tissue-Based Therapy
Small Interfering RNA
atrial natriuretic factor receptor A
Cell Cycle
Carrier Proteins
Cell Death
Cell Proliferation

Keywords

  • Differentiation
  • ESCs
  • Knockdown
  • Label free quantification
  • Natriuretic peptide receptor A
  • Pluripotency
  • Proteome

ASJC Scopus subject areas

  • Cell Biology
  • Cancer Research

Cite this

New Proteomic Insights on the Role of NPR-A in Regulating Self-Renewal of Embryonic Stem Cells. / Magdeldin, Sameh; Yamamoto, Tadashi; Tooyama, Ikuo; Mohamed, Essam.

In: Stem Cell Reviews and Reports, Vol. 10, No. 4, 01.08.2014, p. 561-572.

Research output: Contribution to journalArticle

Magdeldin, Sameh ; Yamamoto, Tadashi ; Tooyama, Ikuo ; Mohamed, Essam. / New Proteomic Insights on the Role of NPR-A in Regulating Self-Renewal of Embryonic Stem Cells. In: Stem Cell Reviews and Reports. 2014 ; Vol. 10, No. 4. pp. 561-572.
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