Haematopoietic stem cells (HSCs) reside in specialized microenvironments within the bone marrow, termed the endosteal and vascular niches. Winkler et al. report that E-selectin, an adhesion molecule expressed by endothelial cells, is a critical component of the vascular niche, where it controls HSC proliferation and chemosensitivity (Nat. Med. 18, 1651–1657; 2012).

The authors observed that HSCs cycled more slowly in E-selectin-knockout mice, as a result of increased HSC quiescence and self-renewal capacity. Transplantation of wild-type fetal livers into E-selectin-deficient mice demonstrated that the E-selectin effects were not intrinsic to the HSCs, but were instead attributable to the absence of E-selectin from the endothelial cells of the bone marrow microenvironment. HSC damage, bone marrow suppression and neutropenia are among the adverse effects of cancer therapies. In vivo mouse experiments established that loss or inhibition of E-selectin renders HSCs more resistant to chemotherapy by inducing their quiescence and by increasing their self-renewal potential, and also allows faster blood leukocyte recovery following irradiation. Although the regulation of HSC proliferation by endothelial E-selectin was shown to be independent of its canonical ligands, the identity of the HSC molecule mediating these effects remains unclear.

Nevertheless, these findings contribute to our understanding of HSC regulation by the vascular niche, and highlight blocking of E-selectin as a potential strategy to alleviate the HSC-damaging side-effects of anti-cancer treatments.