Single-cell Sequencing of Immune and Non-immune Cells from Murine Autoimmune Myocarditic Hearts

Our long-term goal is to determine the immune mechanisms of dilated cardiomyopathy (DCM) and identify strategies for its treatment and prevention. Myocarditis is a common occurrence in children and adolescents that can lead to dilated cardiomyopathy. Since it is difficult to identify the triggers of this complex disease, mechanistic understanding of DCM pathogenesis may create avenues to develop new treatment strategies. Toward this end, we have been engaged in delineating the autoimmune pathways underlying the development of DCM using various mouse models of myocarditis that resemble human disease. One such model is Coxsackievirus B3 (CVB)-induced myocarditis in A/J mice that show two distinct phases of disease, but occur in continuum. While, the acute, infectious phase (up to ~10 days post-infection) is marked by viremia and infiltrations in the hearts, infectious virions become undetected during the chronic phase (~beyond 18 days post-infection), and animals develop DCM. The latter phenotype can occur over a period of ~60 to 90 days, and hitherto, it has been a challenge to determine the underlying reasons. To unravel the complexity of this disease, we leaned towards the single cell RNA sequencing technology (SC RNA seq) that would allow us to discover novel cellular subpopulations that may go beyond our traditional understanding of immune and non-immune cells, and also to identify the transcriptome signatures in the development of DCM. The project is in progress, and any code or processed data along with the relevant publications will be up here soon.