Genetic profiling and surface proteome analysis of human atrial stromal cells and rat ventricular epicardium-derived cells reveals novel insights into their cardiogenic potential

Stem Cell Res. 2017 Dec:25:183-190. doi: 10.1016/j.scr.2017.11.006. Epub 2017 Nov 7.

Abstract

Epicardium-derived cells (EPDC) and atrial stromal cells (ASC) display cardio-regenerative potential, but the molecular details are still unexplored. Signals which induce activation, migration and differentiation of these cells are largely unknown. Here we have isolated rat ventricular EPDC and rat/human ASC and performed genetic and proteomic profiling. EPDC and ASC expressed epicardial/mesenchymal markers (WT-1, Tbx18, CD73, CD90, CD44, CD105), cardiac markers (Gata4, Tbx5, troponin T) and also contained phosphocreatine. We used cell surface biotinylation to isolate plasma membrane proteins of rEPDC and hASC, Nano-liquid chromatography with subsequent mass spectrometry and bioinformatics analysis identified 396 rat and 239 human plasma membrane proteins with 149 overlapping proteins. Functional GO-term analysis revealed several significantly enriched categories related to extracellular matrix (ECM), cell migration/differentiation, immunology or angiogenesis. We identified receptors for ephrin and growth factors (IGF, PDGF, EGF, anthrax toxin) known to be involved in cardiac repair and regeneration. Functional category enrichment identified clusters around integrins, PI3K/Akt-signaling and various cardiomyopathies. Our study indicates that EPDC and ASC have a similar molecular phenotype related to cardiac healing/regeneration. The cell surface proteome repository will help to further unravel the molecular details of their cardio-regenerative potential and their role in cardiac diseases.

Keywords: Cell surface proteomics; Epicardium-derived cells; Human atrial stromal cells.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cell Differentiation
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism
  • Heart Atria / cytology*
  • Heart Atria / metabolism
  • Heart Ventricles / cytology*
  • Heart Ventricles / metabolism
  • Humans
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Pericardium / cytology*
  • Pericardium / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Platelet-Derived Growth Factor / genetics
  • Platelet-Derived Growth Factor / metabolism
  • Proteome / genetics*
  • Proteome / metabolism
  • Proteomics
  • Rats
  • Rats, Wistar
  • Signal Transduction
  • Stromal Cells / cytology*
  • Stromal Cells / metabolism

Substances

  • Platelet-Derived Growth Factor
  • Proteome
  • Epidermal Growth Factor
  • Phosphatidylinositol 3-Kinases