The concentration of retinoic acid determines the differentiated cell types formed by a teratocarcinoma cell line

Retinoic acid (RA) can induce the differentiation of teratocarcinoma cells in culture (S. Strickland and V. Mahdavi, 1978, Cell 15, 393-403; E. M. V. Jones-Villeneuve, M. W. McBurney, K. A. Rogers, and V. I. Kalnins, 1982, J. Cell. Biol. 94, 253-262). With the teratocarcinoma cell line, P19S1801A1 (O1A1), the differentiated cell types formed from cell aggregates exposed to RA are dependent on the concentration of drug used in the treatment. Cultures exposed to low concentrations (10(-9)M) are characterized by an abundance of cardiac muscle. Skeletal muscle becomes abundant at higher drug concentrations (10(-8)M) with neurons and astroglia appearing at very high concentrations (10(-7) to 10(-5) M). These results suggest that during normal embryogenesis, the commitment of pluripotent cells to particular developmental avenues may be determined in part by concentration gradients of substances such as retinoids.