Biology of Isl1+ cardiac progenitor cells in development and disease.

The LIM-homeodomain transcription factor Islet-1 (Isl1) marks a cell population which makes a substantial contribution to the embryonic heart. Isl1 expression is downregulated as soon as the cells adopt a differentiated phenotype, suggesting that this transcription factor delineates a cardiogenic progenitor cell population. Taking advantage of this developmental lineage marker, we have identified in the postnatal heart a novel cardiac cell type, which is capable of self-renewal and readily differentiates into mature cardiomyocytes. Utilization of embryonic stem (ES) cells that harbour knock-ins of reporter genes into the endogenous Isl1 locus will enable us to isolate Isl1+ cardiac progenitors from mouse and human ES cell systems during in vitro cardiogenesis. These genetic cell-based systems should allow the direct identification of signalling pathways which guide formation, renewal and diversification of Isl1+ cardiogenic progenitors into distinct heart cell lineages, and would complement in vitro studies in the mouse embryo during cardiac development.