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Analysis of Physiologic E-Selectin-Mediated Leukocyte Rolling on Microvascular Endothelium
14:16

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Published on: February 11, 2009

Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self renewal and chemoresistance

Ingrid G Winkler1, Valérie Barbier, Bianca Nowlan

  • 1Stem Cells and Cancer Group, Mater Medical Research Institute, South Brisbane, Queensland, Australia. iwinkler@mmri.mater.org.au

Nature Medicine
|October 23, 2012
PubMed

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.

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