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Identification of a clonally expanding haematopoietic compartment in bone marrow
Author(s) -
Wang Lin,
Benedito Rui,
Bixel M Gabriele,
Zeuschner Dagmar,
Stehling Martin,
Sävendahl Lars,
Haigh Jody J,
Snippert Hugo,
Clevers Hans,
Breier Georg,
Kiefer Friedemann,
Adams Ralf H
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2012.308
Subject(s) - biology , haematopoiesis , bone marrow , identification (biology) , compartment (ship) , immunology , computational biology , genetics , cancer research , stem cell , oceanography , botany , geology
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.