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Age-dependent modulation of vascular niches for haematopoietic stem cells
Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.;Univ Munster, Fac Med, D-48149 Munster, Germany..
Max Planck Inst Mol Biomed, Dept Tissue Morphogenesis, D-48149 Munster, Germany.;Univ Munster, Fac Med, D-48149 Munster, Germany..
Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
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2016 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 532, no 7599, 380-+ p.Article in journal (Refereed) PublishedText
Abstract [en]

Blood vessels define local microenvironments in the skeletal system, play crucial roles in osteogenesis and provide niches for haematopoietic stem cells(1-6). The properties of nicheforming 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-beta (PDGFR beta)-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 PDGFR beta-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.

Place, publisher, year, edition, pages
2016. Vol. 532, no 7599, 380-+ p.
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:uu:diva-296853DOI: 10.1038/nature17638ISI: 000374424700034PubMedID: 27074508OAI: oai:DiVA.org:uu-296853DiVA: diva2:940241
Funder
Max Planck SocietyEU, European Research Council, AdG 339409EU, European Research Council, AdG 294556Knut and Alice Wallenberg FoundationSwedish Cancer Society
Available from: 2016-06-20 Created: 2016-06-20 Last updated: 2016-06-20Bibliographically approved

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Betsholtz, Christer
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