Definition of a cell surface signature for human cardiac progenitor cells after comprehensive comparative transcriptomic and proteomic characterization

Sci Rep. 2019 Mar 15;9(1):4647. doi: 10.1038/s41598-019-39571-x.

Abstract

Adult cardiac progenitor/stem cells (CPC/CSC) are multipotent resident populations involved in cardiac homeostasis and heart repair. Assisted by complementary RNAseq analysis, we defined the fraction of the CPC proteome associable with specific functions by comparison with human bone marrow mesenchymal stem cells (MSC), the reference population for cell therapy, and human dermal fibroblasts (HDF), as a distant reference. Label-free proteomic analysis identified 526 proteins expressed differentially in CPC. iTRAQ analysis confirmed differential expression of a substantial proportion of those proteins in CPC relative to MSC, and systems biology analysis defined a clear overrepresentation of several categories related to enhanced angiogenic potential. The CPC plasma membrane compartment comprised 1,595 proteins, including a minimal signature of 167 proteins preferentially or exclusively expressed by CPC. CDH5 (VE-cadherin), OX2G (OX-2 membrane glycoprotein; CD200), GPR4 (G protein-coupled receptor 4), CACNG7 (calcium voltage-gated channel auxiliary subunit gamma 7) and F11R (F11 receptor; junctional adhesion molecule A; JAM-A; CD321) were selected for validation. Their differential expression was confirmed both in expanded CPC batches and in early stages of isolation, particularly when compared against cardiac fibroblasts. Among them, GPR4 demonstrated the highest discrimination capacity between all cell lineages analyzed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD
  • Biomarkers
  • Cadherins
  • Calcium Channels
  • Cell Adhesion Molecules
  • Cell Differentiation / physiology*
  • Gene Expression Profiling / methods
  • Heart / growth & development*
  • Humans
  • Mesenchymal Stem Cells / metabolism
  • Multipotent Stem Cells / metabolism
  • Myocytes, Cardiac / metabolism*
  • Proteome / genetics
  • Proteomics / methods
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Transcriptome / genetics

Substances

  • Antigens, CD
  • Biomarkers
  • CACNG7 protein, human
  • Cadherins
  • Calcium Channels
  • Cell Adhesion Molecules
  • F11R protein, human
  • GPR4 protein, human
  • Proteome
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • cadherin 5
  • antigens, CD200