Master cells that give rise to the three main cell types in a human heart have been discovered by Harvard Stem Cell Institute scientists working independently at two Harvard-affiliated hospitals. Together they found that a single progenitor stem cell differentiates into cells that cause a heart to beat, that make up its internal surface, and form its blood vessels.

The master cells arise during an early stage of embryo growth. As-yet-undiscovered signals then stimulate them to form the main building blocks of the heart, the first identifiable organ in the development of human life. Once started, that life-sustaining muscular pump beats more than 2,500 million times during an average lifetime.

The Harvard research teams tracked the entire process in mouse embryo cells as they grew in glass lab dishes.

The newly identified progenitor cells “offer new prospects for drug discovery and suggest a novel strategy for regeneration of cardiovascular [heart and blood vessel] tissue,” says Kenneth Chien, director of both the Harvard Stem Cell Institute’s cardiovascular disease program and Massachusetts General Hospital’s center for cardiac research. Until now, it was believed that the three sets of heart cells developed from separate ancestors. “Now we have a new model for heart development in which a single multipotent cell can diversify into three lineages,” Chien notes.

“The mechanism of cardiogenesis [heart formation] has fascinated biologists for two centuries,” points out Stuart Orkin, a Harvard Stem Cell Institute researcher who led a separate team at Children’s Hospital Boston. “Despite beliefs that the different cells had distinct origins, recent animal experiments have suggested that a large proportion of cells in the mature heart share a common ancestry. To investigate this, we isolated cardiac progenitor cells from early stage mouse embryos and followed their differentiation. Expectedly, the majority of these cells differentiated spontaneously into muscle cells that expand and contract the heart’s chambers. But, surprisingly, a subset of the cells adapted a smooth muscle cell fate.” This accounted for two of the three major building blocks coming from a single source. The third cell type was identified by Chien’s team at Mass General Hospital.