Haematopoietic stem cell differentiation promotes the release of prominin‐1/CD133‐containing membrane vesicles—a role of the endocytic–exocytic pathway

Abstract The differentiation of stem cells is a fundamental process in cell biology and understanding its mechanism might open a new avenue for therapeutic strategies. Using an ex vivo co‐culture system consisting of human primary haematopoietic stem and progenitor cells growing on multipotent mesenchymal stromal cells as a feeder cell layer, we describe here the exosome‐mediated release of small membrane vesicles containing the stem and cancer stem cell marker prominin‐1 (CD133) during haematopoietic cell differentiation. Surprisingly, this contrasts with the budding mechanism underlying the release of this cholesterol‐binding protein from plasma membrane protrusions of neural progenitors. Nevertheless, in both progenitor cell types, protein–lipid assemblies might be the essential structural determinant in the release process of prominin‐1. Collectively, these data support the concept that prominin‐1‐containing lipid rafts may host key determinants necessary to maintain stem cell properties and their quantitative reduction or loss may result in cellular differentiation.