Tracking Spatio-Temporal Dynamics of Scar Formation at Single-Cell Resolution (A01 (P01))

• Subject Area: Cardiology, Angiology ; General Genetics and Functional Genome Biology ; Bioinformatics and Theoretical Biology ; Immunology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422681845

We will build on our spatio-temporal analysis of scar formation in the adult mouse to investigate the dynamics of lesion remodelling after myocardial infarction of varying penetrance in neonatal mice on postnatal days 1 (P1) and 7 (P7). On P1, cardiac muscle is able to regenerate, potentially without leaving a scar, due to cardiomyocyte de-differentiation, proliferation, and replacement of injured tissue, with concomitant scar resolution. The heart loses this ability by P7, and lesioned myocardium forms a scar thereafter. We hypothesise that differences in inflammatory responses and immune regulatory functions determine the occurrence of full cardiac regeneration versus formation of a permanent scar. In particular, changes in inflammatory or immune-regulatory functions, coupled with fibroblast activation in the regenerative versus the non-regenerative myocardium, may be critical modulators of lesion remodeling and fibrosis. Our long-term vision is to link knowledge gained from the P1-P7 neonatal model systems to adult hearts, in order to develop novel lesion-modifying and anti-fibrotic intervention.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1425: Heterocellular Nature of Cardiac Lesions: Identities, Interactions, Implications
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Project Head: Professor Dr. Dominic Grün