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EPCR expression marks UM171-expanded CD34+ cord blood stem cells

Iman Fares, Jalila Chagraoui, Bernhard Lehnertz, Tara MacRae, Nadine Mayotte, Elisa Tomellini, Léo Aubert, Philippe P. Roux and Guy Sauvageau

Key points

  • EPCR is a reliable surface marker that detects human HSCs in culture.

  • EPCR is required for HSPC function in vivo.

Abstract

A small subset of human cord blood CD34+ cells express endothelial protein c receptor (EPCR/CD201/PROCR) when exposed to hematopoietic stem cell (HSC) self-renewal agonist UM171. Here we show that EPCR-positive UM171-treated cells, as opposed to EPCR-negative cells, exhibit robust multi-lineage repopulation and serial reconstitution ability in immunocompromised mice. In contrast to other stem cell markers such as CD38, EPCR expression is maintained when cells are introduced in culture, irrespective of UM171 treatment. Although engineered overexpression of EPCR fails to reproduce the effects of UM171 on HSC activity, its expression is required for the repopulating activity of human HSCs. Altogether, our results indicate that EPCR is a reliable and cell culture-compatible marker of UM171-expanded human cord blood HSCs.

  • Submitted November 21, 2016.
  • Accepted March 27, 2017.