Functional Epigenetic Modulation of Cardiac Fibroblasts (A02 (P02))

• Subject Area: Cardiology, Angiology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 422681845

We will combine multimodal single cell and spatial analysis with fibroblast lineage tracing to decode common and distinct trajectories of fibroblast activation and transdifferentiation in cardiac lesions resulting from different insults. The inclusion of non-fibroblast cells will allow prediction of heterocellular interactions that promote scar formation. We will use CRISPR-based functional epigenetic methods to modulate the activity and spatial interactions of regulatory elements. For efficient delivery of these constructs to fibroblast, we will optimise AAV vectors and delivery routes. This will allow testing of the impact of functional epigenetic modulation on scar formation in vivo. To assess the translational relevance of functional epigenetic modulation in human fibroblasts, and to validate heterocellular interactions, we will use human iPSC-derived fibroblasts and non- fibroblasts. In summary, this project will decode the trajectories of fibroblast activation on the epigenome and transcriptome levels, and establish functional epigenetic methods to modulate these trajectories, with a vison of modifying scar properties.

• 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. Ralf Gilsbach