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          Institute: MPI für molekulare Biomedizin     Collection: Jahrbuch 2017 (publ. 2016, arch)     Display Documents

ID: 732139.0, MPI für molekulare Biomedizin / Jahrbuch 2017 (publ. 2016, arch)
Distinct bone marrow blood vessels differentially regulate haematopoiesis
Authors:Itkin, T.; Gur-Cohen, S.; Spencer, J. A.; Schajnovitz, A.; Ramasamy, S. K.; Kusumbe, A. P.; Ledergor, G.; Jung, Y.; Milo, I.; Poulos, M. G.; Kalinkovich, A.; Ludin, A.; Kollet, O.; Shakhar, G.; Butler, J. M.; Rafii, S.; Adams, R. H.; Scadden, D. T.; Lin, C. P.; Lapidot, T.
Date of Publication (YYYY-MM-DD):2016-04
Title of Journal:Nature
Issue / Number:7599
Start Page:323
End Page:+
Review Status:Internal review
Audience:Not Specified
Abstract / Description: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.
Free Keywords:stem-cell quiescence; progenitor cells; rapid mobilization; endothelial-cells; sdf-1 release; stromal cells; niche; megakaryocytes; engraftment; integrity; Science & Technology - Other Topics
External Publication Status:published
Document Type:Article
Communicated by:Jeanine Müller-Keuker
Affiliations:MPI für molekulare Biomedizin
External Affiliations:Lapidot, T (reprint author), Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel.; Lin, CP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA.; Lin, CP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Syst Biol, Boston, MA 02114 USA. charles_lin@hms.harvard.edu; tsvee.lapidot@weizmann.ac.il %G English
Identifiers:ISSN:0028-0836 %R 10.1038/nature17624 [ID No:1]
URL:<Go to ISI>://WOS:000374424700024 [ID No:2]
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