3,5,3'-TRIIODO-L-THYRONINE INDUCES CARDIAC MYOCYTE DIFFERENTIATION BUT NOT NEURONAL DIFFERENTIATION IN P19 TERATOCARCINOMA CELLS IN A DOSE-DEPENDENT MANNER

P19 teratocarcinoma cells differentiate into neurons or muscle when treated with varying doses of retinoic acid, dimethylsulfoxide, thioguanine or butyrate. We induced cardiac differentiation in P19 cells by treating them with 3,5,3'-Triiodo-L-Thyronine (T-3). P19 cells received doses of T-3 ranging from 30 pM to 300 nM. The beating colonies were counted, and a dose response curve showed that the optimal concentration of T-3 was 30 nM. The colonies beat rhythmically for 4-6 weeks, and the cardiac myocytes showed clearly evident cardiac-specific organelles such as nexuses and atrial granules. No evidence of neuronal or skeletal muscle differentiation was seen with any of the concentrations of T-3 used. Reverse transcription-polymerase chain reaction showed these cells to express the cardiac ventricular specific marker myosin light chain 2V. T-3 is capable of inducing P19 cells to differentiate, in a dose related manner, into spontaneously beating cardiac myocytes identified as such on the basis of ultrastructural criteria. The induction of differentiation is accompanied by expression of cardiao-specific genes. These findings suggest that perhaps genes bearing thyroid response elements in their promoter regions play an important role in the cardiac differentiation induced by T-3 in P19 teratocarcinoma cells, (C) 1994 Academic Press, Inc.