Transcriptional profiling reveals fundamental differences in iPS-derived progenitors of endothelial cells (PECs) versus adult circulating EPCs

TL;DR

This study compares gene expression profiles of iPS-derived PECs and adult circulating EPCs, revealing fundamental differences that could improve cell-based therapies for vascular diseases.

Contribution

It provides a comprehensive transcriptional comparison between iPS-derived PECs and adult EPCs, clarifying their distinct molecular identities.

Findings

EPCs and PECs have distinct gene expression profiles.

VEGF is essential for PEC differentiation from mesodermal precursors.

RNAseq analysis shows these cell populations are fundamentally different.

Abstract

There are a number of different stem cell sources that have the potential to be used as therapeutics in vascular degenerative diseases. On the one hand, there are so called endothelial progenitor cells (EPCs), which are typically derived from adult blood. They carry the marker CD34, but the true nature and definition of EPCs is still controversial. On the other hand, there are embryonic precursors of endothelial cells (PECs), which also express CD34, and can be differentiated from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) in vitro. In this study, it was aimed to compare these two different CD34 positive cell populations by full genome transcriptional profiling (RNAseq). To this end, we firstly optimised a PEC differentiation protocol and found that vascular endothelial growth factor (VEGF) is critical for the transition of cells from mesodermal precursors to PECs. Additionally, principal component analysis (PCA) of RNAseq data showed that blood-derived EPCs clustered far from iPS-derived PECs which illustrates these populations are fundamentally different. This data will be useful to better define these cell populations and facilitating the translation of regenerative approaches in this field as well as providing potentially novel diagnostic tools.