Advanced search
1 file | 3.16 MB Add to list

Identification of a clonally expanding haematopoietic compartment in bone marrow

(2013) EMBO JOURNAL. 32(2). p.219-230
Author
Organization
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.
Keywords
STEM-CELL NICHE, NORMAL MOUSE FEMUR, perivascular cells, haematopoiesis, endothelium, bone marrow, SKELETAL DEVELOPMENT, PROGENITOR CELLS, IN-VIVO, VEGF, ANGIOGENESIS, MICE, HOMEOSTASIS, RECONSTITUTION

Downloads

  • (...).pdf
    • full text
    • |
    • UGent only
    • |
    • PDF
    • |
    • 3.16 MB

Citation

Please use this url to cite or link to this publication:

MLA
Wang, Lin, Rui Benedito, M Gabriele Bixel, et al. “Identification of a Clonally Expanding Haematopoietic Compartment in Bone Marrow.” EMBO JOURNAL 32.2 (2013): 219–230. Print.
APA
Wang, Lin, Benedito, R., Bixel, M. G., Zeuschner, D., Stehling, M., Sävendahl, L., Haigh, J., et al. (2013). Identification of a clonally expanding haematopoietic compartment in bone marrow. EMBO JOURNAL, 32(2), 219–230.
Chicago author-date
Wang, Lin, Rui Benedito, M Gabriele Bixel, Dagmar Zeuschner, Martin Stehling, Lars Sävendahl, Jody Haigh, et al. 2013. “Identification of a Clonally Expanding Haematopoietic Compartment in Bone Marrow.” Embo Journal 32 (2): 219–230.
Chicago author-date (all authors)
Wang, Lin, Rui Benedito, M Gabriele Bixel, Dagmar Zeuschner, Martin Stehling, Lars Sävendahl, Jody Haigh, Hugo Snippert, Hans Clevers, Georg Breier, Friedemann Kiefer, and Ralf H Adams. 2013. “Identification of a Clonally Expanding Haematopoietic Compartment in Bone Marrow.” Embo Journal 32 (2): 219–230.
Vancouver
1.
Wang L, Benedito R, Bixel MG, Zeuschner D, Stehling M, Sävendahl L, et al. Identification of a clonally expanding haematopoietic compartment in bone marrow. EMBO JOURNAL. 2013;32(2):219–30.
IEEE
[1]
L. Wang et al., “Identification of a clonally expanding haematopoietic compartment in bone marrow,” EMBO JOURNAL, vol. 32, no. 2, pp. 219–230, 2013.
@article{3196233,
  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.},
  author       = {Wang, Lin and Benedito, Rui and Bixel, M Gabriele and Zeuschner, Dagmar and Stehling, Martin and Sävendahl, Lars and Haigh, Jody and Snippert, Hugo and Clevers, Hans and Breier, Georg and Kiefer, Friedemann and Adams, Ralf H},
  issn         = {0261-4189},
  journal      = {EMBO JOURNAL},
  keywords     = {STEM-CELL NICHE,NORMAL MOUSE FEMUR,perivascular cells,haematopoiesis,endothelium,bone marrow,SKELETAL DEVELOPMENT,PROGENITOR CELLS,IN-VIVO,VEGF,ANGIOGENESIS,MICE,HOMEOSTASIS,RECONSTITUTION},
  language     = {eng},
  number       = {2},
  pages        = {219--230},
  title        = {Identification of a clonally expanding haematopoietic compartment in bone marrow},
  url          = {http://dx.doi.org/10.1038/emboj.2012.308},
  volume       = {32},
  year         = {2013},
}

Altmetric
View in Altmetric
Web of Science
Times cited: