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Early Events Leading to Erythroid Differentiation in Mouse Friend Cells Revealed by Cell Fusion Experiments¹

Institute of Applied Microbiology, University of Tokyo, Bunkyo-ku, Tokyo 113, Japan

Cell fusion with two genetically marked Friend (murine erythroleukemia) cells has made it possible to characterize the very early events leading to erythroid differentiation, particularly the nature of reactions initiated by inducers such as dimethyl sulfoxide. We have found that brief exposure of Friend cells to dimethyl sulfoxide (as well as butyric acid or hexamethylene-bisacetamide) induces an early cellular activity required for erythroid differentiation which is detected only by fusion with ultraviolet-irradiated cells. The induction process of this activity consists of at least two distinct stages. In the first stage, the reaction proceeds without supply of metabolites from the medium and exhibits sensitivity to tumor promoters. The second stage is tightly coupled to cellular metabolic activity, notably protein synthesis. Under normal conditions, the induced activity is short-lived, suggesting turnover of the molecules responsible for this activity. There appears to be a signal produced following dimethyl sulfoxide pulse which acts as an inducer for this activity. The signal remains active for as long as 40 hr when protein synthesis is blocked.

¹ This research was supported by grants from the Nissan Science Foundation, the Ministry of Education of Japan, and the Ministry of Health and Welfare of Japan.

² To whom requests for reprints should be addressed.

Received 10/ 3/83. Accepted 1/19/84.