Proteome Changes during Transition from Human Embryonic to Vascular Progenitor Cells

Research output: Contribution to journalArticle

Authors

  • Konstantinos Tsolis
  • Eleni Bagli
  • katerina Kanaki
  • Sofia Zografou
  • Sebastien Carpentier
  • Ekaterini Bei
  • Savvas Christoforidis
  • Michalis Zervakis
  • Theodore Fotsis
  • Anastassios Economou

Colleges, School and Institutes

External organisations

  • Division of Biomedical Research, Institute of Molecular Biology and Biotechnology - FORTH, 45110 Ioaninna, Greece
  • Department of Protein structure and Proteomics Facility, Institute of Molecular Biology and Biotechnology - FORTH, 70013 Iraklio, Crete, Greece
  • Department of Biology, University of Crete, 70013 Iraklio, Crete, Greece
  • Department of Biosystems Engineering, KU Leuven - University of Leuven and SYBIOMA, KU Leuven facility for Systems Biology Based Mass Spectrometry, B-3000 Leuven Belgium
  • School of Electronic and Computer Engineering, Technical University of Crete, 73100 Chania, Greece
  • SYBIOMA, KU Leuven facility for Systems Biology Based Mass Spectrometry, B-3000 Leuven Belgium
  • Department of Microbiology and Immunology, Rega Institute for Medical Research, Laboratory of Molecular Bacteriology, KU Leuven - University of Leuven, B-3000 Leuven, Belgium
  • Laboratory of Biological Chemistry, Medical School, University of Ioannina, 45110 Ioannina, Greece
  • University of Birmingham, School of Biosciences, UK

Abstract

Human embryonic stem cells (hESCs) are promising in regenerative medicine (RM) due to their differentiation plasticity and proliferation potential. However, a major challenge in RM is the generation of a vascular system to support nutrient flow to newly synthesized tissues. Here we refined an existing method to generate tight vessels by differentiating hESCs in CD34+ vascular progenitor cells using chemically defined media and growth conditions. We selectively purified these cells from CD34– outgrowth populations also formed. To analyze these differentiation processes, we compared the proteomes of the hESCs with those of the CD34+ and CD34– populations using high resolution mass spectrometry, label-free quantification, and multivariate analysis. Eighteen protein markers validate the differentiated phenotypes in immunological assays; nine of these were also detected by proteomics and show statistically significant differential abundance. Another 225 proteins show differential abundance between the three cell types. Sixty-three of these have known functions in CD34+ and CD34– cells. CD34+ cells synthesize proteins implicated in endothelial cell differentiation and smooth muscle formation, which support the bipotent phenotype of these progenitor cells. CD34– cells are more heterogeneous synthesizing muscular/osteogenic/chondrogenic/adipogenic lineage markers. The remaining >150 differentially abundant proteins in CD34+ or CD34– cells raise testable hypotheses for future studies to probe vascular morphogenesis.

Details

Original languageEnglish
JournalJournal of Proteome Research
Early online date5 May 2016
Publication statusE-pub ahead of print - 5 May 2016

Keywords

  • endothelial progenitor cells, hESCs, vascular cell differentiation, CD34+, angiogenesis, comparative proteomics, multivariate analysis, PLS