title: Identification of a clonally expanding haematopoietic compartment in bone marrow.
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.
authors.affiliation: Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, University of Münster, Münster, Germany.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Benedito
authors.forename: M Gabriele
authors.initials: MG
authors.lastname: Bixel
authors.forename: Dagmar
authors.initials: D
authors.lastname: Zeuschner
authors.forename: Martin
authors.initials: M
authors.lastname: Stehling
authors.forename: Lars
authors.initials: L
authors.lastname: Sävendahl
authors.forename: Jody J
authors.initials: JJ
authors.lastname: Haigh
authors.forename: Hugo
authors.initials: H
authors.lastname: Snippert
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.forename: Georg
authors.initials: G
authors.lastname: Breier
authors.forename: Friedemann
authors.initials: F
authors.lastname: Kiefer
authors.forename: Ralf H
authors.initials: RH
authors.lastname: Adams
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology / Q000502:physiology; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology* / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D002999:Clone Cells / Q000502:physiology; D005260:Female; D006410:Hematopoiesis / Q000502:physiology*; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological