Differentiation of embryonic heart tube-derived cardiac progenitor cells into pacemaker-like cells

Abstract

At present, the mechanisms governing the development of cardiac pacemaking and conduction system are not well understood. To provide evidence for the derivation of pacemaker cells and the signal that induce and maintain the cells in the developing heart,Nkx2.5+ cardiac progenitor cells (CPCs) from embryonic heart tubes of rats were induced by endothelin-1 to differentiate towards cardiac pacemaker cells. After Nkx2.5+ CPCs were treated with endothelin-1, the cells all displayed spontaneous beating and spontaneously electrical activity. In particular, around 38% of the treated cells generated spontaneous sinus node-like action potentials. The induced cells appeared some junction structures and a few of myofibrils which uniformly were organized poorly without Z lines. Moreover, Nkx2.5+ CPCs expressed gap junction, pacemaker channel and α-sarcomeric actin proteins after ET-1 treatment. These ultrastructural hallmarks and molecule expression of the induced cells are similar to that of the sinoatrial node cells which are isolated from hearts. After transplantation of the induced cells into left ventriculr wall of rat, the idioventricular beat rate was increased markedly. In conclusion, our study support the notion that the node cells originate from Nkx2.5+ CPCs present in embryonic heart tubes and endothelin-1 is involved in diversification of the cardiomyogenic progenitors toward the node cells.