MODULATED EXPRESSION OF THE EPIDERMAL GROWTH FACTOR-LIKE HOMEOTIC PROTEIN DLK INFLUENCES STROMAL-CELL-PRE-B-CELL INTERACTIONS, STROMAL CELLADIPOGENESIS, AND PRE-B-CELL INTERLEUKIN-7 REQUIREMENTS

A close relationship exists between adipocyte differentiation of strom al cells and their capacity to support hematopoiesis. The molecular ba sis for this is unknown. We have studied whether dlk, an epidermal gro wth factor-like molecule that intervenes in adipogenesis and fetal liv er hematopoiesis, affects both stromal cell adipogenesis and B-cell ly mphopoiesis in an established pre-B-cell culture system. Pre B cell cu ltures require both soluble interleukin-7 (IL-7) and interactions with stromal cells to promote cell growth and prevent B-cell maturation or apoptosis. We found that BALB/c 3T3 fibroblasts express dlk and funct ion as stromal cells. Transfection of these cells with antisense dlk d ecreased dlk expression and increased insulin-induced adipocytic diffe rentiation. When antisense transfectants were used as stroma, IL-7 was no longer required to support the growth of pre-B cells and prevent m aturation or apoptosis. Antisense dlk transfectants of S10 stromal cel ls also promoted pre-B-cell growth in the absence of IL-7. These resul ts show that modulation of dlk on stromal cells can influence their ad ipogenesis and the IL-7 requirements of the pre-B cells growing in con tact with them. These results indicate that dlk influences differentia tion signals directed both to the stromal cells and to the lymphocyte precursors, suggesting that dlk may play an important role in the bone marrow hematopoietic environment.