UM171 treatment of CD34-enriched CB cells induces the expansion of EPCR⁺ cells. EPCR⁻ and EPCR^low cells are present within CD34⁺CD38⁻CD49f^Med HSCs, but only EPCR⁺ cells also express a more primitive phenotype defined by the expression of both CD90 and CD133. Injection of EPCR⁺ sorted cells, but not EPCR^−/low populations, into immunodeficient mice results in human engraftment with multilineage reconstitution.