Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow
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Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow
| Title: | Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow |
| Author: |
Yu, Vionnie W.C.; Saez, Borja; Cook, Colleen; Lotinun, Sutada; Pardo-Saganta, Ana; Wang, Ying-Hua; Lymperi, Stefania; Ferraro, Francesca; Raaijmakers, Marc H.G.P.; Wu, Joy Y.; Zhou, Lan; Rajagopal, Jayaraj; Kronenberg, Henry M.; Baron, Roland; Scadden, David T.
Note: Order does not necessarily reflect citation order of authors. |
| Citation: | Yu, V. W., B. Saez, C. Cook, S. Lotinun, A. Pardo-Saganta, Y. Wang, S. Lymperi, et al. 2015. “Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow.” The Journal of Experimental Medicine 212 (5): 759-774. doi:10.1084/jem.20141843. http://dx.doi.org/10.1084/jem.20141843. |
| Full Text & Related Files: |
4419348.pdf (4.939Mb; PDF) 
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| Abstract: | Production of the cells that ultimately populate the thymus to generate α/β T cells has been controversial, and their molecular drivers remain undefined. Here, we report that specific deletion of bone-producing osteocalcin (Ocn)-expressing cells in vivo markedly reduces T-competent progenitors and thymus-homing receptor expression among bone marrow hematopoietic cells. Decreased intrathymic T cell precursors and decreased generation of mature T cells occurred despite normal thymic function. The Notch ligand DLL4 is abundantly expressed on bone marrow Ocn+ cells, and selective depletion of DLL4 from these cells recapitulated the thymopoietic abnormality. These data indicate that specific mesenchymal cells in bone marrow provide key molecular drivers enforcing thymus-seeding progenitor generation and thereby directly link skeletal biology to the production of T cell–based adaptive immunity. |
| Published Version: | doi:10.1084/jem.20141843 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419348/pdf/ |
| Terms of Use: | This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA |
| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845294 |
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