Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self renewal and chemoresistance
Menée à l'aide d'un modèle murin, cette étude met en évidence le rôle joué par une molécule d'adhésion cellulaire, la sélectine E, dans le micro-environnement des cellules souches hématopoïétiques et suggère qu'un blocage temporaire de cette molécule permettrait de protéger les cellules souches des effets d'une chimiothérapie ou d'une radiothérapie
The microenvironment, or niche, surrounding a stem cell largely governs its cellular fate. Two anatomical niches for hematopoietic stem cells (HSCs) have been reported in the bone marrow, but a distinct function for each of these niches remains unclear. Here we report a new role for the adhesion molecule E-selectin expressed exclusively by bone marrow endothelial cells in the vascular HSC niche. HSC quiescence was enhanced and self-renewal potential was increased in E-selectin knockout (Sele−/−) mice or after administration of an E-selectin antagonist, demonstrating that E-selectin promotes HSC proliferation and is a crucial component of the vascular niche. These effects are not mediated by canonical E-selectin ligands. Deletion or blockade of E-selectin enhances HSC survival threefold to sixfold after treatment of mice with chemotherapeutic agents or irradiation and accelerates blood neutrophil recovery. As bone marrow suppression is a severe side effect of high-dose chemotherapy, transient blockade of E-selectin is potentially a promising treatment for the protection of HSCs during chemotherapy or irradiation.
Nature Medicine 2012