Abstract 686: Notch Activation Increases Following Injury In The Adult Heart
The adult heart has a limited regenerative capacity. Intense interest has focused on the definition of factors or signaling pathways that promote myocardial repair and regeneration. To identify and decipher the pathways that direct the proliferation and differentiation of cardiac progenitor cells in the adult mouse heart, an in vitro culture system was utilized. Using a Notch indicator transgenic mouse and flow cytometry, we isolated a population of CD31−/CD45− cells with activated Notch that increases following cryoinjury. Using genome wide transcriptome analysis to compare these cells isolated from an uninjured animal versus cells isolated day 5 post cryoinjury we observed a pronouced induction of cardiac specific genes. The CD31−/CD45−cells with activated Notch isolated from an uninjured adult mouse are highly proliferative in culture and appear to be immortalized. They spontaneously differentiate into fibroblasts, myofibroblasts and smooth muscle cells as determined by immunohistochemisty. These cells also exhibit cardiac specific markers following chemically induced differentiation. These results identify a population of cells that have the potential to regenerate an injured mouse heart, thus highlighting the possible utility of perturbations within the Notch pathway to regulate proliferation and differentiation in the adult mouse heart.