TY - JOUR
T1 - Dissecting the cellular landscape and transcriptome network in viral myocarditis by single-cell RNA sequencing
AU - Lasrado, Ninaad
AU - Borcherding, Nicholas
AU - Arumugam, Rajkumar
AU - Starr, Timothy K.
AU - Reddy, Jay
N1 - Publisher Copyright:
© 2022 The Author(s)
PY - 2022/3/18
Y1 - 2022/3/18
N2 - 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.
AB - 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.
KW - Pathophysiology
KW - Systems biology
KW - Transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85124765629&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2022.103865
DO - 10.1016/j.isci.2022.103865
M3 - Article
AN - SCOPUS:85124765629
SN - 2589-0042
VL - 25
JO - iScience
JF - iScience
IS - 3
M1 - 103865
ER -