Proteome Changes during Transition from Human Embryonic to Vascular Progenitor Cells

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• 作者：Konstantinos C. Tsolis ; Eleni Bagli ; Katerina Kanaki ; Sofia Zografou ; Sebastien Carpentier ; Ekaterini S. Bei ; Savvas Christoforidis ; Michalis Zervakis ; Carol Murphy ; Theodore Fotsis ; Anastassios Economou
• 刊名：Journal of Proteome Research
• 出版年：2016
• 出版时间：June 3, 2016
• 年：2016
• 卷：15
• 期：6
• 页码：1995-2007
• 全文大小：680K
• 年卷期：0
• ISSN：1535-3907

文摘

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.