Role of endothelial antigen ESAM in activated hematopoietic stem cells

Through their differentiation and self-renewal capabilities, hematopoietic stem cells (HSCs) supply the vast amounts of blood cells needed throughout life. The use of surface markers to purify HSCs has been promoted. After bone marrow injury, however, HSCs are activated, and the expression pattern of HSC-related antigens changes dramatically. Endothelial cell-selective adhesion molecule (ESAM), an immunoglobulin superfamily protein, was originally identified as an endothelium-specific molecule. We recently reported ESAM as a new HSC marker. In the present study, we demonstrate the monitoring of ESAM levels to provide a useful indicator of HSC activation. Expression levels of ESAM clearly mirrored shifts in HSC status between quiescence and activation, and the shifts were more prominent than those of other HSC-related antigens. ESAMHi HSCs were active in the cell cycle while maintaining a high capacity for long-term reconstitution. More than 80% of ESAMHi HSCs were located near endothelium in the bone marrow after 5-FU treatment. Furthermore, ESAM is functionally important for HSCs to re-establish homeostatic hematopoiesis. Our data demonstrate ESAM expression levels to be useful for monitoring HSC status, tracing the proliferation of HSCs in vivo and understanding the molecular events underlying HSC activation.