in vivo reprogramming of non myocardial cells during cardiac regeneration

• Applicant: Dr. Sven Reischauer
• Subject Area: Developmental Biology ; Cell Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 496770602

The aim of this research project is to elucidate essential mechanisms of cardiac regeneration. In mammals, including humans, most tissues respond to injury by the activation of a fibrotic program, which in turn leads to the formation of a functionally inert scar or organ fibrosis. Mechanistically, this is based on transdifferentiation of connective tissue cells, which alter the affected tissue by secretion and deposition of fibrotic extracellular matrix, leading to a functional demise. This process particularly affects the heart and is a major cause of various cardiac diseases.In contrast to mammals, zebrafish belong to the regenerative species. In these, even most severe cardiac injuries are healed by the formation of a functional regenerate. A central component of this process involves the connective tissue cells, which, unlike those of mammals, hardly transdifferentiate but are transiently reprogrammed to support regeneration by activating a regenerative gene program.The specific aim of this project is both to investigate the diversity of cardiac stromal (non-muscle) cells and to elucidate the mechanisms involved in their regenerative reprogramming. The starting point of our study is a unique model in zebrafish that, similar to mammals, responds to cardiac injury with transdifferentiation of connective tissue and endothelial cells, but not with regenerative reprogramming and functional recovery.As a result, we expect our study to provide a deeper understanding of regenerative processes and new approaches in the development of regenerative therapies.

• DFG Programme: Research Grants