Abstract 011: Transcriptional Basis Of Epicardial Progenitor Cell Activation During Heart Development, Regeneration And Repair

The epicardium encapsulates the heart and functions as a source of multipotent progenitor cells and paracrine factors essential for cardiac development and repair. Injury of the adult heart results in reactivation of epicardial progenitor cells, which reengages a developmental gene program, but the underlying transcriptional basis has not been delineated. We established a mouse embryonic heart organ culture and gene expression system that facilitated the identification of epicardial enhancers activated during heart development and injury. Epicardial activation of these enhancers depends on a combinatorial transcriptional code centered on C/EBP, HOX, MEIS, and GRAINYHEAD families of transcription factors. Furthermore, disruption of C/EBP signaling in the adult epicardium reduced injury-induced neutrophil infiltration and improved cardiac function. These findings reveal a transcriptional basis for epicardial progenitor cell activation during heart development and injury, providing a platform for enhancing cardioprotection and regeneration.