BoneKEy Reports | BoneKEy Watch
The role of E-selectin in the vascular HSC niche
DOI:10.1038/bonekey.2012.258
E-selectin is an adhesion molecule expressed only by bone marrow endothelial cells. In order to elucidate its function in the vascular hematopoietic stem cell (HSC) niche, Winkler et al. compared HSC turnover in wild-type mice with that in E-selectin and P-selectin knockout mice.1
Only E-selectin knockout mice showed significantly reduced HSC turnover. Three separate assays were then used to confirm that E-selectin knockout mice had 30% more quiescent HSCs than wild-type mice, suggesting that E-selectin increased HSC quiescence and gave the cells a greater potential for self-renewal.
Only endothelial cells within the bone marrow express E-selectin, which therefore acts exclusively within the HSC vascular niche to accelerate HSC proliferation, an effect that is cell extrinsic and mediated by the microenvironment within the bone marrow. The mechanism of action involves interaction between E-selectin and noncanonical ligands on HSCs. In mice, the major E-selectin ligands appear to be glycosphingolipids, but the identity of the ligand in humans remains to be discovered.
E-selectin knockout mice showed faster blood recovery after irradiation, and GMI-1070, an E-selectin agonist, was also shown to enhance HSC chemoresistance.
Editor’s comment: Transient administration of a small synthetic E-selectin antagonist to block proliferative signaling by the vascular niche could become a novel therapeutic approach to protect HSCs against the damage induced by radiotherapy or cytotoxic chemotherapy.
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