Regulation of lineage commitment of hematopoietic stem cells by the stromal cells

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To know the regulatory mechanism of lineage commitment of hematopoietic stem cells by the stromal cells in bone marrow, the sorted stem cells were cocultured on 2 established stromal cells. TBR59 stromal cells support myelopoisis and lymphopoiesis of the sorted stem cells. Another cell line, TBR31-1 was shown to specifically induce B-lymphopoiesis. In both cocultures, the commitment of differentiation of the stem cells toward myeloid and lymphoid was observed without exogenously added soluble factors. Finally we obtained two immortalized stem-like cell lines depending on the stromal cells. One is B-lymphoid stem-like cell line and the other is stem cell-like cell lines with surface markers and both cell lines can be differentiated.We examined molecules involved in the interaction between the stromal and stem cells and found that c-Kit and its ligand, SCF,VLA-4, an integrin, or VCAM-1, a ligand for VLA-4, are necessary factors. To know other factors involved in the stromal cells, we made monoclonal antibodies to each stromal cell line and obtained specific monoclonal antibodies to one type of the stromal cells. Then, the expression cDNA library made from the two cell lines was used for screening of the antigenic molecules recognized by these antibodies.