Dissecting the cellular landscape and transcriptome network in viral myocarditis by single-cell RNA sequencing

Ninaad Lasrado; Nicholas Borcherding; Rajkumar Arumugam; Timothy K Starr; Jay Reddy

doi:10.1016/j.isci.2022.103865

Dissecting the cellular landscape and transcriptome network in viral myocarditis by single-cell RNA sequencing

iScience. 2022 Feb 2;25(3):103865. doi: 10.1016/j.isci.2022.103865. eCollection 2022 Mar 18.

Authors

Ninaad Lasrado¹, Nicholas Borcherding², Rajkumar Arumugam¹, Timothy K Starr³, Jay Reddy¹

Affiliations

¹ School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, USA.
² Department of Pathology and Immunology, Washington University in St. Louis, St Louis, MO 63130, USA.
³ Department of Obstetrics and Gynecology, University of Minnesota, Minneapolis, MN 55455, USA.

Abstract

Coxsackievirus B3 (CVB3)-induced myocarditis is commonly employed to study viral pathogenesis in mice. Chronically affected mice may develop dilated cardiomyopathy, which may involve the mediation of immune and nonimmune cells. To dissect this complexity, we performed single-cell RNA sequencing on heart cells from healthy and myocarditic mice, leading us to note significant proportions of myeloid cells, T cells, and fibroblasts. Although the transcriptomes of myeloid cells were mainly of M2 phenotype, the Th17 cells, CTLs, and Treg cells had signatures critical for cytotoxic functions. Fibroblasts were heterogeneous expressing genes important in fibrosis and regulation of inflammation and immune responses. The intercellular communication networks revealed unique interactions and signaling pathways in the cardiac cellulome, whereas myeloid cells and T cells had upregulated unique transcription factors modulating cardiac remodeling functions. Together, our data suggest that M2 cells, T cells, and fibroblasts may cooperatively or independently participate in the pathogenesis of viral myocarditis.

Keywords: Pathophysiology; Systems biology; Transcriptomics.