Single cell profiling of salamander heart under homeostasis and after cryoinjury.

ABSTRACT: Heart disease is the leading cause of mortality worldwide due to the limited regenerative capacity of the mammalian heart. Myocardial infarction causes massive cardiomyocyte apoptosis that is replaced by a fibrotic scar. In contrast to mammals, certain vertebrates such as fish and amphibians can regenerate cardiac muscle without scarring. Here, we established a cryoinjury model in the salamander species, Pleurodeles waltl. We performed single-cell RNA sequencing to profile the salamander heart and identified CLDN6 as a specific marker of epicardium, the outermost mesothelial layer enclosing the heart. Notably, lineage tracing experiments showed differentiation of CLDN6+ epicardium-derived cell intermediates into cardiomyocytes in response to injury. Additionally, scRNA-seq experiments suggested a differentiation trajectory that describes epicardial cell to myocyte conversion. Furthermore, ablation of these intermediates with Clostridium perfringens enterotoxin (CPE) blocked cardiac regeneration.

ORGANISM(S): Pleurodeles waltl

PROVIDER: GSE180914 | GEO | 2022/02/21

REPOSITORIES: GEO