Yu, Vionnie W.C.Saez, BorjaCook, ColleenLotinun, SutadaPardo-Saganta, AnaWang, Ying-HuaLymperi, StefaniaFerraro, FrancescaRaaijmakers, Marc H.G.P.Wu, Joy Y.Zhou, LanRajagopal, JayarajKronenberg, HenryBaron, RolandScadden, David2015-12-042015Yu, 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.20141843.0022-1007http://nrs.harvard.edu/urn-3:HUL.InstRepos:23845294Production 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.en-USJournal Article2015-12-0410.1084/jem.20141843