ABSTRACT
The molecular mechanisms that direct the migration of early T lymphocyte progenitors to the thymus are unknown. We show here that P-selectin is expressed by thymic endothelium and that lymphoid progenitors in bone marrow and thymus bind P-selectin. Parabiosis, competitive thymus reconstitution and short-term homing assays indicated that P-selectin and its ligand PSGL-1 are functionally important components of the thymic homing process. Accordingly, thymi of mice lacking PSGL-1 contained fewer early thymic progenitors and had increased empty niches for prothymocytes compared with wild-type mice. Furthermore, the number of resident thymic progenitors controls thymic expression of P-selectin, suggesting that regulation of P-selectin expression by a thymic 'niche occupancy sensor' may be used to direct progenitor access.
Subject(s)
Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/metabolism , Membrane Glycoproteins/metabolism , P-Selectin/metabolism , T-Lymphocytes/cytology , T-Lymphocytes/metabolism , Animals , Cell Movement , Endothelium/immunology , Endothelium/metabolism , Hematopoietic Stem Cells/immunology , In Vitro Techniques , Ligands , Membrane Glycoproteins/deficiency , Membrane Glycoproteins/genetics , Mice , Mice, Inbred C57BL , Mice, Knockout , P-Selectin/genetics , T-Lymphocytes/immunology , Thymus Gland/cytology , Thymus Gland/immunology , Thymus Gland/metabolismABSTRACT
Cells from adult bone marrow participate in the regeneration of damaged skeletal myofibers. However, the relationship of these cells with the various hematopoietic and nonhematopoietic cell types found in bone marrow is still unclear. Here we show that the progeny of a single cell can both reconstitute the hematopoietic system and contribute to muscle regeneration. Integration of bone marrow cells into myofibers occurs spontaneously at low frequency and increases with muscle damage. Thus, classically defined single hematopoietic stem cells can give rise to both blood and muscle.
