A Novel Molecular and Functional Stemness Signature Assessing Human Cord Blood-Derived Endothelial Progenitor Cell Immaturity

PLoS One. 2016 Apr 4;11(4):e0152993. doi: 10.1371/journal.pone.0152993. eCollection 2016.

Abstract

Endothelial Colony Forming Cells (ECFCs), a distinct population of Endothelial Progenitor Cells (EPCs) progeny, display phenotypic and functional characteristics of endothelial cells while retaining features of stem/progenitor cells. Cord blood-derived ECFCs (CB-ECFCs) have a high clonogenic and proliferative potentials and they can acquire different endothelial phenotypes, this requiring some plasticity. These properties provide angiogenic and vascular repair capabilities to CB-ECFCs for ischemic cell therapies. However, the degree of immaturity retained by EPCs is still confused and poorly defined. Consequently, to better characterize CB-ECFC stemness, we quantified their clonogenic potential and demonstrated that they were reprogrammed into induced pluripotent stem cells (iPSCs) more efficiently and rapidly than adult endothelial cells. Moreover, we analyzed the transcriptional profile of a broad gene panel known to be related to stem cells. We showed that, unlike mature endothelial cells, CB-ECFCs expressed genes involved in the maintenance of embryonic stem cell properties such as DNMT3B, GDF3 or SOX2. Thus, these results provide further evidence and tools to appreciate EPC-derived cell stemness. Moreover this novel stem cell transcriptional signature of ECFCs could help better characterizing and ranging EPCs according to their immaturity profile.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers
  • Cell Differentiation / genetics*
  • Cell Line
  • Cell Self Renewal / genetics*
  • Cells, Cultured
  • Cellular Reprogramming
  • Colony-Forming Units Assay
  • Endothelial Cells / cytology
  • Endothelial Cells / metabolism
  • Endothelial Progenitor Cells / cytology*
  • Endothelial Progenitor Cells / metabolism*
  • Female
  • Fetal Blood / cytology*
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Human Embryonic Stem Cells / cytology
  • Human Embryonic Stem Cells / metabolism
  • Humans
  • Induced Pluripotent Stem Cells / cytology
  • Induced Pluripotent Stem Cells / metabolism
  • Transcriptome*
  • Young Adult

Substances

  • Biomarkers

Grants and funding

Support from the French National Research Agency (ANR) grant MATRIXCELL (ANR-2010-TECS-010-02). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.