title: Age-dependent modulation of vascular niches for haematopoietic stem cells.
abstract: 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.
authors.affiliation: Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
authors.forename: Anjali P
authors.initials: AP
authors.lastname: Kusumbe
authors.affiliation: Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
authors.forename: Saravana K
authors.initials: SK
authors.lastname: Ramasamy
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Itkin
authors.affiliation: Vascular Biology Program, Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden.
authors.forename: Maarja Andaloussi
authors.initials: MA
authors.lastname: Mäe
authors.affiliation: Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
authors.forename: Urs H
authors.initials: UH
authors.lastname: Langen
authors.affiliation: Vascular Biology Program, Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden.|Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institute, Scheeles väg 2, SE-171 77 Stockholm, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Betsholtz
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Tsvee
authors.initials: T
authors.lastname: Lapidot
authors.affiliation: Max-Planck-Institute for Molecular Biomedicine, Department of Tissue Morphogenesis, and University of Münster, Faculty of Medicine, D-48149 Münster, Germany.
authors.forename: Ralf H
authors.initials: RH
authors.lastname: Adams
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D001160:Arterioles / Q000166:cytology / Q000502:physiology*; D001842:Bone and Bones / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D002196:Capillaries / Q000166:cytology / Q000502:physiology*; D002452:Cell Count; D042783:Endothelial Cells / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D008297:Male; D051379:Mice; D010012:Osteogenesis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism; D015398:Signal Transduction; D019089:Stem Cell Factor / Q000378:metabolism; D055153:Stem Cell Niche
chemical_list: D051793:Hypoxia-Inducible Factor 1; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D051880:Receptors, Notch; D019089:Stem Cell Factor; D020797:Receptor, Platelet-Derived Growth Factor beta