Myology 2005 - Tuesday, May 10th - Plenary lecture "Heart cell lineage diversification in physiology and disease : the islet-1 cardiovascular progenitor story   

 

The heart is composed of diverse muscle and non-muscle cell lineages: atrial/ventricular/conduction system/smooth muscle myocytes, endocardial/endothelial, and valvular. Congenital heart diseases can arise from defects in the pathways for heart lineage specification (Pashmforoush et al, Cell 2004), and human degenerative diseases can arise in a subset of ventricular and pacemaker cells, (for review see Chien and Karsenty, Cell, 2005). The pathways that guide heart cell lineage diversification are relatively obscure, as the primordial heart precursor cells have not been clearly identified. Recently, we reported the identification of isl1+ cardiac progenitors in post-natal rat, mouse, and human heart muscle (Laugwitz et al Nature, 2005). A cardiac mesenchymal feeder layer drives progenitor cell renewal, maintaining their triggered differentiation into fully mature cardiomyocyte phenotype in the absence of cell fusion. A tamoxifen-inducible Cre/lox system allows selective in vivo marking of this progenitor cell population and purification by FACS analysis. In lineage tracing studies with islet-cre knock-in mice, the islet precursors represent master heart progenitors that give rise to all of the major muscle and non-muscle cell lineages, e.g., SA nodal, venous and coronary arterial endothelial/smooth muscle, and valvular. Utilizing mouse ES cells that harbor a knock-in of LacZ into the Isl-1 locus, there is now the feasibility of isolating isl1+ cardiac progenitors from mouse and human ES cell systems during in vitro cardiogenesis. This system should allow the rapid and direct identification of the pathways which guide the formation, renewal, and diversification of islet master heart progenitors into distinct heart cell lineages, and forms a biological foundation for the tissue engineering of specific heart components.