Distinct bone marrow blood vessels differentially regulate haematopoiesis

Tomer Itkin, Shiri Gur-Cohen, Joel A. Spencer, Amir Schajnovitz, Saravana K. Ramasamy, Anjali P. Kusumbe, Guy Ledergor, Yookyung Jung, Idan Milo, Michael G. Poulos, Alexander Kalinkovich, Aya Ludin, Karin Golan, Eman Khatib, Anju Kumari, Orit Kollet, Guy Shakhar, Jason M. Butler, Shahin Rafii, Ralf H. Adams, David T. Scadden, Charles P. Lin () and Tsvee Lapidot ()
Additional contact information
Tomer Itkin: The Weizmann Institute of Science
Shiri Gur-Cohen: The Weizmann Institute of Science
Joel A. Spencer: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School
Amir Schajnovitz: Harvard University
Saravana K. Ramasamy: Max Planck Institute for Molecular Biomedicine, University of Münster
Anjali P. Kusumbe: Max Planck Institute for Molecular Biomedicine, University of Münster
Guy Ledergor: The Weizmann Institute of Science
Yookyung Jung: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School
Idan Milo: The Weizmann Institute of Science
Michael G. Poulos: Weill Cornell Medical College
Alexander Kalinkovich: The Weizmann Institute of Science
Aya Ludin: The Weizmann Institute of Science
Karin Golan: The Weizmann Institute of Science
Eman Khatib: The Weizmann Institute of Science
Anju Kumari: The Weizmann Institute of Science
Orit Kollet: The Weizmann Institute of Science
Guy Shakhar: The Weizmann Institute of Science
Jason M. Butler: Weill Cornell Medical College
Shahin Rafii: Weill Cornell Medical College
Ralf H. Adams: Max Planck Institute for Molecular Biomedicine, University of Münster
David T. Scadden: Harvard University
Charles P. Lin: Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School
Tsvee Lapidot: The Weizmann Institute of Science

Nature, 2016, vol. 532, issue 7599, 323-328

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/nature17624

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