Characterization of progenitors of endothelial cells (PECs)

There are a number of different stem cell sources that have the potential to be used as therapeutics in vascular degenerative diseases such as diabetic retinopathy. 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 which can be differentiated from embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) in vitro. Furthermore, a subpopulation of human umbilical cord endothelial cells (HUVECs) has also been shown to express CD34. In this study, It was aimed to compare these three different CD34 positive cell populations by full genome transcriptional profiling (RNAseq). To this end I firstly optimised a PEC differentiation protocol and found that VEGF is critical for the transition from mesodermal precursors to PECs. Secondly, I found signalling pathways that regulate CD34 expression in HUVECs and showed a close correlation between CD34 expression and the endothelial tip/stalk cell phenotypes. Thirdly, principal component analysis (PCA) of RNAseq data showed that blood-derived EPCs are fundamentally different from iPS-derived PECs. Lastly, I also identified from RNAseq data number of potentially novel PEC markers. Once validated such novel markers of PECs and EPCs will be useful to better define these cell populations, facilitating the translation of regenerative approaches in this field as well as providing potentially novel diagnostic tools