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Blood vessels define local microenvironments in the skeletal system, play crucial roles in osteogenesis and provide niches for haematopoietic stem cells. The properties of niche-forming vessels and their changes in the ageing organism remain incompletely understood. Here we show that Notch signalling in endothelial cells leads to the expansion of haematopoietic stem cell niches in bone, which involves increases in CD31-positive capillaries and platelet-derived growth factor receptor-β (PDGFRβ)-positive perivascular cells, arteriole formation and elevated levels of cellular stem cell factor. Although endothelial hypoxia-inducible factor signalling promotes some of these changes, it fails to enhance vascular niche function because of a lack of arterialization and expansion of PDGFRβ-positive cells. In ageing mice, niche-forming vessels in the skeletal system are strongly reduced but can be restored by activation of endothelial Notch signalling. These findings indicate that vascular niches for haematopoietic stem cells are part of complex, age-dependent microenvironments involving multiple cell populations and vessel subtypes.

Original publication

DOI

10.1038/nature17638

Type

Journal article

Journal

Nature

Publication Date

13/04/2016

Volume

532

Pages

380 - 384

Addresses

Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.

Keywords

Bone and Bones, Arterioles, Capillaries, Hematopoietic Stem Cells, Endothelial Cells, Animals, Mice, Receptor, Platelet-Derived Growth Factor beta, Antigens, CD31, Stem Cell Factor, Cell Count, Signal Transduction, Aging, Osteogenesis, Male, Hypoxia-Inducible Factor 1, Receptors, Notch, Stem Cell Niche