Functional definition of endothelial progenitors by PROCR and PDGFRA co-expression
Cassandra Styke1, Simranpreet Kaur2, Seen-Ling Sim1
1The University of Queensland Frazer Institute, The University of Queensland, Brisbane, QLD, 4102, Australia.
Angiogenesis
|August 1, 2026
Summary
Researchers identified refined endothelial progenitor cells (rEPCs) expressing PROCR and PDGFRA, which possess superior blood vessel formation capacity compared to other progenitor cells. This finding clarifies the definition of endothelial progenitor cells.
Area of Science:
- Vascular Biology
- Cellular and Molecular Medicine
- Hematopoiesis
Background:
- The precise identity and function of endothelial progenitor cells (EPCs) contributing to blood vessel formation in vivo are not fully established.
- Existing studies define putative EPCs using diverse markers and methodologies, leading to conflicting definitions.
Purpose of the Study:
- To reconcile divergent reports on EPC definitions by investigating the overlap of Protein C Receptor (PROCR) and Platelet-Derived Growth Factor Receptor Alpha (PDGFRA) expression.
- To functionally characterize EPCs expressing both PROCR and PDGFRA, termed refined EPCs (rEPCs).
Main Methods:
- Single-cell RNA-sequencing and flow cytometry were employed to analyze cell populations.
- Functional assays, including clonogenic capacity and engraftment potential, were performed.
- Lineage tracing studies were conducted in murine models of homeostasis and injury.
Main Results:
- PROCR and PDGFRA expression largely overlapped with previously identified murine CD34+CD31low endovascular progenitors (EVPs).
- PROCR+PDGFRA+ EPCs (rEPCs) exhibited enhanced clonogenic capacity, engraftment potential, and differentiation into endothelial cells compared to PROCR-PDGFRA- EVPs.
- Similar PROCR and PDGFRA expression patterns were observed in human aorta, and human placental endothelial cells with these markers showed increased clonogenic capacity.
Conclusions:
- Overlapping PROCR and PDGFRA expression effectively narrows the population of endothelial progenitor cells with true functional capacity.
- This study refines the definition of EPCs, identifying rEPCs as key contributors to vascular development and repair.
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
01:15Differentiation of Common Myeloid Progenitor Cells
Common myeloid progenitors (CMPs) are oligopotent cells that can differentiate into granulocytes and macrophages. Granulocytes and macrophages are essential for protecting the body against bacterial, viral, or fungal infections. They migrate from the bone marrow into the circulating blood to reach specific tissue sites where they differentiate and help in immune surveillance. However, they survive only for a few days and must be continuously made available to the organism to maintain a robust...
01:34Production of Formed Elements
Hemangioblasts are multipotent stem cells originating from the mesoderm. They give rise to hematopoietic stem cells (HSCs), which undergo hematopoiesis to produce all the formed elements of blood. This process is regulated by a complex network of hematopoietic growth factors, including transcription factors, growth factors, and cytokines. These factors stimulate the HSCs to divide and differentiate, though some HSCs remain undifferentiated to maintain a self-renewing pool.
Most HSCs commit to...
Most HSCs commit to...