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Nature. 2016 Apr 21;532(7599):323-8. doi: 10.1038/nature17624. Epub 2016 Apr 13.

Distinct bone marrow blood vessels differentially regulate haematopoiesis.

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Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA.
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Harvard Stem Cell Institute, Cambridge, Massachusetts 02114, USA.
Center for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis and Faculty of Medicine, University of Münster, D-48149 Münster, Germany.
Internal Medicine Department, Tel-Aviv Sourasky Medical Center, Tel-Aviv 64239, Israel.
Department of Genetic Medicine, Weill Cornell Medical College, New York, New York 10065, USA.


Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.

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