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.,
The Journal of Experimental Medicine
Department of Hematology

Yu, V. W. C., Saez, B., Cook, C., Lotinun, S., Pardo-Saganta, A., Wang, Y.-H., … Scadden, D. T. (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