Stem Cell Reviews and Reports

, Volume 10, Issue 4, pp 561–572 | Cite as

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

  • Sameh Magdeldin
  • Tadashi Yamamoto
  • Ikuo Tooyama
  • Essam M. Abdelalim


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.


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


Competing interests

The authors have declared no conflict of interest.


This work was supported by JSPS (Japan Society for Promotion of Science) Grant-in-Aid for scientific research (B) to SM (23790933), and standard JSPS grant for foreign researcher (P 14105) to SM from Ministry of Education, Culture, Sports, Science and Technology of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Supplementary material

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Supplemental Table 1 (XLSX 145 kb)
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Supplemental Table 2 (XLSX 33 kb)


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Sameh Magdeldin
    • 1
    • 2
  • Tadashi Yamamoto
    • 1
  • Ikuo Tooyama
    • 3
  • Essam M. Abdelalim
    • 3
    • 4
    • 5
  1. 1.Department of Structural Pathology Institute of Nephrology, Graduate School of Medical and Dental SciencesNiigata UniversityTokyoJapan
  2. 2.Department of Physiology, Faculty of Veterinary MedicineSuez Canal UniversityIsmailiaEgypt
  3. 3.Molecular Neuroscience Research CenterShiga University of Medical ScienceOtsuJapan
  4. 4.Qatar Biomedical Research InstituteQatar Foundation, Education CityDohaQatar
  5. 5.Department of Cytology and Histology, Faculty of Veterinary MedicineSuez Canal UniversityIsmailiaEgypt

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