DNA-SYNTHESIS AND MULTINUCLEATION IN EMBRYONIC STEM CELL-DERIVED CARDIOMYOCYTES

The proliferative capacity of embryonic stem (ES) cell-derived cardiom yocytes was assessed. Enriched preparations of cardiomyocytes were iso lated by microdissection of the cardiogenic regions of cultured embryo id bodies. The identity of the isolated cells was established by immun ocytology, and mitotic activity was monitored by [H-3]thymidine incorp oration and pulse-chase experiments. ES-derived cardiomyocytes were mi totically active and predominantly mononucleated at 11 days after card iogenic induction. By 21 days postinduction, cardiomyocyte DNA synthes is was markedly decreased, with a concomitant increase in the percenta ge of multinucleated cells. Interestingly, the duration of active card iomyocyte reduplication in the ES system appeared to be roughly simila r to that observed during normal murine cardiogenesis. Given these obs ervations, as well as the genetic tractability of ES cells, ES-derived cardiogenesis might provide a useful in vitro system with which to as sess the molecular regulation of the cardiomyocyte cell cycle.