Ischemic heart Failure (IHF) is a leading cause of hospitalization and mortality in Europe. This unmet challenge asks for a better understanding of the mechanisms causing myocardial tissue damage and the development of new therapeutic approaches supporting cardiac repair. The immune system plays a decisive role for initial inflammatory responses following cardiac damage and subsequent regenerative responses. However, the interplay between immune cells and cardiomyocytes/cardiac progenitor cells within the myocardium is not well understood. We aim to explore the spatial and temporal communication between cardiac myocytes, cardiac stem cells and innate immune cells during IHF. We will use high-end transcriptional profiling involving single-cell RNA-seq / tomo-seq combined with mouse genetics and large animal models to identify new factors involved in cellular interactions responsible for cardiac remodeling. Furthermore, we want to understand the function of crucial mediators of cardiomyocyte-innate immune cell interactions, the Reg-family of cytokines, for post-ischemic damage control and tissue repair. Our research will supply new approaches for the manipulation of cell-cell interactions in the failing heart. All model organisms capable of cardiac regeneration rely on immune cells to orchestrate different waves of inflammation, matrix deposition, angiogenesis and cardiomyocyte proliferation. Hence, therapeutic manipulation of local immune cell-dependent processes in the damaged heart might shift the balance between extensive scarring, minimal defect healing and regeneration.