Junctional adhesion molecule-A, JAM-A, is a novel cell-surface marker for long-term repopulating hematopoietic stem cells

Abstract

AbstractJunctional adhesion molecule-A (JAM-A/JAM-1/F11R) is a cell adhesion molecule expressed in epithelial and endothelial cells, and also hematopoietic cells, such as leukocytes, platelets, and erythrocytes. Here, we show that JAM-A is expressed at a high level in the enriched hematopoietic stem cell (HSC) fraction; that is, CD34+c-Kit+ cells in embryonic day 11.5 (E11.5) aorta-gonod-mesonephros (AGM) and E11.5 fetal liver (FL), as well as c-Kit+Sca-1+Lineage− (KSL) cells in E14.5 FL, E18.5FL, and adult bone marrow (BM). Although the percentage of JAM-A+ cells in those tissues decreases during development, the expression in the HSC fraction is maintained throughout life. Colony-forming assays reveal that multilineage colony-forming activity in JAM-A+ cells is higher than that in JAM-A− cells in the enriched HSC fraction in all of those tissues. Transplantation assays show that long-term reconstituting HSC (LTR-HSC) activity is exclusively in the JAM-A+ population and is highly enriched in the JAM-A+ cells sorted directly from whole BM cells by anti–JAM-A antibody alone. Together, these results indicate that JAM-A is expressed on hematopoietic precursors in various hematopoietic tissues and is an excellent marker to isolate LTR-HSCs.