Letter | Published:

Age-dependent modulation of vascular niches for haematopoietic stem cells

Nature volume 532, pages 380384 (21 April 2016) | Download Citation

  • A Corrigendum to this article was published on 14 September 2016


Blood vessels define local microenvironments in the skeletal system, play crucial roles in osteogenesis and provide niches for haematopoietic stem cells1,2,3,4,5,6. 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.

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We thank M. Schiller for technical assistance, A. Starsichova for help with bone sample processing, M. Stehling for fluorescence-activated cell sorting (FACS), S. Volkery for microscopy, and M. Vanlandewijck and K. Nahar for help with PdgfbiOE-EC bones. Funding was provided by the Max Planck Society, the University of Münster, the DFG cluster of excellence ‘Cells in Motion’, and the European Research Council (AdG 339409 ‘AngioBone’). This research was partly supported by a joint grant from the Ministry of Science, Technology & Space, Israel, DKFZ Germany, ERC AdG 294556 ‘BBBarrier’, the Knut and Alice Wallenberg Foundation and the Swedish Cancer Foundation.

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

    • Anjali P. Kusumbe
    • , Saravana K. Ramasamy
    • , Urs H. Langen
    •  & Ralf H. Adams
  2. Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel

    • Tomer Itkin
    •  & Tsvee Lapidot
  3. Vascular Biology Program, Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden

    • Maarja Andaloussi Mäe
    •  & Christer Betsholtz
  4. Department of Medical Biochemistry and Biophysics, Division of Vascular Biology, Karolinska Institute, Scheeles väg 2, SE-171 77 Stockholm, Sweden

    • Christer Betsholtz


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A.P.K., S.K.R. and R.H.A. designed experiments and interpreted results. A.P.K. and S.K.R. organized and conducted most experiments, including generation and characterization of mouse lines, imaging, flow cytometric analysis and transplantations. T.I. and T.L. designed and performed transplantation experiments. M.A.M. and C.B. generated and provided samples from PdgfbiOE-EC mice. A.P.K and U.H.L. analysed Efnb2 and NICD-Cre mice. A.P.K., S.K.R. and R.H.A. wrote the manuscript.

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The authors declare no competing financial interests.

Corresponding authors

Correspondence to Anjali P. Kusumbe or Ralf H. Adams.

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