Identification of a clonally expanding haematopoietic compartment in bone marrow |
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| Authors: | Lin Wang Rui Benedito M Gabriele Bixel Dagmar Zeuschner Martin Stehling Lars Sävendahl Jody J Haigh Hugo Snippert Hans Clevers Georg Breier Friedemann Kiefer Ralf H Adams |
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| Institution: | 1. Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, and Faculty of Medicine, University of Münster, , Münster, Germany;2. Electron Microscopy and Flow Cytometry Units, Max Planck Institute for Molecular Biomedicine, , Münster, Germany;3. Division of Pediatric Endocrinology, Department of Women's and Children's Health, Astrid Lindgren Children's Hospital, Karolinska Institutet, , Stockholm, Sweden;4. Vascular Cell Biology Unit, VIB Department for Molecular Biomedical Research, and UGhent Department for Molecular Biology, , Ghent, Belgium;5. Hubrecht Institute, KNAW, University Medical Center Utrecht, , Utrecht, The Netherlands;6. Medical Faculty Carl Gustav Carus, Institute of Pathology, Dresden University of Technology, , Dresden, Germany;7. Mammalian Cell Signaling Laboratory, Max Planck Institute for Molecular Biomedicine, , Münster, Germany |
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| Abstract: | In mammals, postnatal haematopoiesis occurs in the bone marrow (BM) and involves specialized microenvironments controlling haematopoietic stem cell (HSC) behaviour and, in particular, stem cell dormancy and self‐renewal. While these processes have been linked to a number of different stromal cell types and signalling pathways, it is currently unclear whether BM has a homogenous architecture devoid of structural and functional partitions. Here, we show with genetic labelling techniques, high‐resolution imaging and functional experiments in mice that the periphery of the adult BM cavity harbours previously unrecognized compartments with distinct properties. These units, which we have termed hemospheres, were composed of endothelial, haematopoietic and mesenchymal cells, were enriched in CD150+ CD48? putative HSCs, and enabled rapid haematopoietic cell proliferation and clonal expansion. Inducible gene targeting of the receptor tyrosine kinase VEGFR2 in endothelial cells disrupted hemospheres and, concomitantly, reduced the number of CD150+ CD48? cells. Our results identify a previously unrecognized, vessel‐associated BM compartment with a specific localization and properties distinct from the marrow cavity. |
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| Keywords: | bone marrow endothelium haematopoiesis perivascular cells |
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