Elucidating cardiac fibroblasts heterogeneity and activation during experimental autoimmune myocarditis using spatial transcriptomics

Dilated cardiomyopathy (DCM), which develops from myocardial inflammation, is frequently linked to a poor prognosis and fatal outcome. Experimental autoimmune myocarditis (EAM) serves as an animal model of CD4⁺ T cells-dependent acute myocarditis that is followed by the development of post-inflammatory DCM. The study's objective was to employ spatial transcriptomics to investigate how cardiac fibroblasts' transcriptional patterns changed during the acute inflammatory phase of EAM. Our spatial transcriptomic analysis on 1545 cardiac fibroblasts enriched spots, in 657 of which fibroblasts were dominant cell population, resulted in identification of six distinct fibroblast subsets, which frequency changed during the acute inflammatory phase of EAM. The observed spatiotemporal colocalization of infiltrating immune cells with fibroblasts during the acute inflammatory phase may indicate that fibroblast activation is associated with, or possibly influenced by, the presence of myeloid cell infiltrates. Our findings suggest that acute myocardial inflammation may trigger a fibroblast-to-myofibroblast transition and a pro-inflammatory transcriptional response in cardiac fibroblasts. New treatment approaches for inflammatory heart disease may be developed with the aid of an understanding of the transcriptomic signatures on the spatial level.