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

Blood. 2017 Jun 22;129(25):3344-3351. doi: 10.1182/blood-2016-11-750729. Epub 2017 Apr 13.

Abstract

A small subset of human cord blood CD34+ cells express endothelial protein C receptor (EPCR/CD201/PROCR) when exposed to the hematopoietic stem cell (HSC) self-renewal agonist UM171. In this article, we show that EPCR-positive UM171-treated cells, as opposed to EPCR-negative cells, exhibit robust multilineage 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / analysis*
  • Antigens, CD34 / analysis*
  • Cell Culture Techniques
  • Cell Proliferation / drug effects
  • Endothelial Protein C Receptor
  • Female
  • Fetal Blood / cytology*
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / drug effects*
  • Humans
  • Indoles / pharmacology*
  • Mice, Inbred NOD
  • Mice, SCID
  • Pyrimidines / pharmacology*
  • Receptors, Cell Surface / analysis*

Substances

  • Antigens, CD
  • Antigens, CD34
  • Endothelial Protein C Receptor
  • Indoles
  • PROCR protein, human
  • Pyrimidines
  • Receptors, Cell Surface
  • UM171 compound

Grant support