Differential expression of endothelial protein C receptor (EPCR) in hematopoietic stem and multipotent progenitor cells in young and old mice

• Published in: Cells & development Vol. 174; p. 203843
• Main Authors: Lin, Dawn S., Trumpp, Andreas
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2023
• Subjects: Aged; Animals; Bone Marrow - metabolism; Endothelial protein C receptor (EPCR); Endothelial Protein C Receptor - genetics; Endothelial Protein C Receptor - metabolism; Hematopoietic stem cell (HSC); Hematopoietic Stem Cells - metabolism; HSC ageing; Humans; Mice; Multi-parameter flow cytometry; Multipotent progenitor (MPP); Multipotent Stem Cells - metabolism; Prospective Studies; Stem cell marker; Multipotent progenitor (MPP); Hematopoietic stem cell (HSC); Endothelial protein C receptor (EPCR); Stem cell marker; HSC ageing; Multi-parameter flow cytometry
• ISSN: 2667-2901; 2667-2901
• DOI: 10.1016/j.cdev.2023.203843

Endothelial protein C receptor (EPCR) has emerged as one of the most conserved and reliable surface markers for the prospective identification and isolation of hematopoietic stem cells (HSCs). Prior studies have consistently demonstrated that EPCR expression enriches HSCs capable of long-term multilineage repopulation in both mouse and human across different hematopoietic tissues, including bone marrow (BM), fetal liver and ex vivo HSC expansion cultures. However, little is known about the expression profiles of EPCR in multipotent progenitor (MPP) populations located immediately downstream of HSCs in the hematopoietic hierarchy and which play a major role in sustaining lifelong blood cell production. Here, we incorporate EPCR antibody detection into a multi-parameter flow cytometric panel, which allows accurate identification of HSCs and five MPP subsets (MPP1-5) in mouse BM. Our data reveal that all MPP populations contain EPCR-expressing cells. Multipotent MPP1 and MPP5 contain higher proportion of EPCR+ cells compared to the more lineage-biased MPP2–4. Notably, high expression of EPCR enriches phenotypic HSC and MPP5, but not MPP1. Comparison of EPCR expression profiles between young and old BM reveals ageing mediated expansion of EPCR-expressing cells only in HSCs, but not in any of the MPP populations. Collectively, our study provides a comprehensive characterization of the surface expression pattern of EPCR in mouse HSC and MPP1–5 cells during normal and aged hematopoiesis. •EPCR is a conserved and reliable phenotypic marker for HSC enrichment.•EPCR expression is heterogenous in mouse MPP populations.•Newly characterized MPP5 population contains high proportion of EPCR-expressing cells.•Ageing mediates preferential expansion of EPCRhi HSCs.