Regulation of myeloid and lymphoid development of hematopoietic stem cells by bone marrow stromal cells.

Development of hematopoietic stem cells is regulated by stromal cells of the bone marrow. Many stromal cell lines have been established from temperature-sensitive SV40 large T-antigen gene transgenic mice and used to examine regulation of the purified stem cells. When the sorted stem cells were cocultured on the stromal cell layers, cobblestone formation was induced by the stromal cells. The cobblestones were formed by finite cell division (8 divisions on average) of sorted Lin- c-Kit+ Sca1+ stem cells committed to myeloid or lymphoid lineages. These stromal cell lines showed variable activities supporting the stem cell development. In one stromal cell line, TBR59, two waves of cobblestone formation committed to either myeloid lineage or lymphoid lineage were induced. TBR31-1, another bone marrow stromal cell line, induced only the cobblestone formation committed to lymphoid lineage. These results indicate that the bone marrow stromal cells selectively induce lineage-specific commitment of the stem cells. Both cobblestone formations require c-Kit function as well as adhesive interaction through VLA4 and VCAM1.