Two monoclonal antibodies identify thymic-repopulating cells in mouse bone marrow.

The progenitor cells in the bone marrow that home to and repopulate the thymus have been incompletely characterized. In particular, it is not clear whether thymocytes differentiate directly from pluripotent hemopoietic stem cells that seed to the thymus, or whether T lymphoid-committed stem cells (prothymocytes) arise in the bone marrow before the thymic migration. In order to resolve this question, we have used mAb specific for cell-surface Ag to identify the bone marrow cells which can seed to and repopulate the thymus of irradiated mice. We report here that the majority of thymic-repopulating cells in mouse bone marrow express low levels of the Thy-1 Ag (Thy-1lo) plus high levels of a newly described Ag termed stem cell Ag (Sca-1). Two distinct populations of thymic-repopulating Thy-1loSca-1+ cells in mouse bone marrow can be discriminated based on expression of any of a number of hemolymphoid lineage-specific (Lin) markers. Thus, Thy-1loLin-Sca-1+ and Thy-1loLin+Sca-1+ fractions of bone marrow contain thymic-repopulating cells. A second Ag, stem cell Ag-2 (Sca-2), is expressed by Thy-1loLin+Sca-1+ cells but not by Thy-1loLin-Sca-1+ cells. The Thy-1loLin-Sca-1+ fraction expresses intermediate levels of the phagocyte glycoprotein-1 Ag, and comprises 30% of the Thy-1loLin- bone marrow cells, which have previously been shown to be highly enriched in pluripotent hemopoietic stem cells. By facilitating the isolation of highly purified subpopulations of bone marrow cells that can repopulate the thymus, Sca-1 and Sca-2 should provide an experimental tool for describing the developmental potential of such bone marrow subsets.