title: Distinct bone marrow blood vessels differentially regulate haematopoiesis.
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.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Tomer
authors.initials: T
authors.lastname: Itkin
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Shiri
authors.initials: S
authors.lastname: Gur-Cohen
authors.affiliation: 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.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Spencer
authors.affiliation: 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.
authors.forename: Amir
authors.initials: A
authors.lastname: Schajnovitz
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis and Faculty of Medicine, University of Münster, D-48149 Münster, Germany.
authors.forename: Saravana K
authors.initials: SK
authors.lastname: Ramasamy
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis and Faculty of Medicine, University of Münster, D-48149 Münster, Germany.
authors.forename: Anjali P
authors.initials: AP
authors.lastname: Kusumbe
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.|Internal Medicine Department, Tel-Aviv Sourasky Medical Center, Tel-Aviv 64239, Israel.
authors.forename: Guy
authors.initials: G
authors.lastname: Ledergor
authors.affiliation: 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.
authors.forename: Yookyung
authors.initials: Y
authors.lastname: Jung
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Idan
authors.initials: I
authors.lastname: Milo
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Poulos
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kalinkovich
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Aya
authors.initials: A
authors.lastname: Ludin
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Orit
authors.initials: O
authors.lastname: Kollet
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Guy
authors.initials: G
authors.lastname: Shakhar
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Butler
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York 10065, USA.
authors.forename: Shahin
authors.initials: S
authors.lastname: Rafii
authors.affiliation: Max Planck Institute for Molecular Biomedicine, Department of Tissue Morphogenesis and Faculty of Medicine, University of Münster, D-48149 Münster, Germany.
authors.forename: Ralf H
authors.initials: RH
authors.lastname: Adams
authors.affiliation: 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.
authors.forename: David T
authors.initials: DT
authors.lastname: Scadden
authors.affiliation: 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.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Lin
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Tsvee
authors.initials: T
authors.lastname: Lapidot
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001158:Arteries / Q000166:cytology / Q000502:physiology; D001808:Blood Vessels / Q000166:cytology* / Q000502:physiology*; D001853:Bone Marrow / Q000098:blood supply*; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002465:Cell Movement; D000066673:Cell Self Renewal; D002470:Cell Survival; D054377:Chemokine CXCL12 / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology; D005260:Female; D006410:Hematopoiesis; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology; D007962:Leukocytes / Q000166:cytology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D064231:Nestin / Q000378:metabolism; D020286:Pericytes / Q000502:physiology; D010539:Permeability; D010949:Plasma / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism
chemical_list: D000950:Antigens, Ly; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C515256:Cxcl12 protein, mouse; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; C577485:Nes protein, mouse; D064231:Nestin; D017382:Reactive Oxygen Species; D019718:Receptors, CXCR4