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

Area of Science:

• Cardiovascular Research
• Immunology
• Genomics

Background:

• Dilated cardiomyopathy (DCM) often follows myocardial inflammation, leading to poor outcomes.
• Experimental autoimmune myocarditis (EAM) models CD4+ T cell-dependent myocarditis preceding DCM.

Purpose of the Study:

• To investigate cardiac fibroblast transcriptional changes during acute EAM using spatial transcriptomics.
• To identify fibroblast subsets and their roles in inflammatory heart disease.

Main Methods:

• Spatial transcriptomic analysis of 1545 cardiac fibroblast-enriched spots in an EAM model.
• Identification and frequency analysis of fibroblast subsets during acute inflammation.

Main Results:

• Six distinct cardiac fibroblast subsets were identified, with changing frequencies during acute EAM.
• Fibroblast activation and a fibroblast-to-myofibroblast transition were observed.
• Spatiotemporal colocalization suggests immune cell infiltrates influence fibroblast activation.

Conclusions:

• Acute myocardial inflammation alters cardiac fibroblast transcriptional patterns.
• Understanding spatial transcriptomic signatures may lead to novel treatments for inflammatory heart disease.