Single-cell transcriptomics reveals zinc and copper ions homeostasis in epicardial adipose tissue of heart failure.

ABSTRACT

Epicardial adipose tissue (EAT) is a unique visceral fat reservoir that shares an immune microenvironment without a distinct boundary with myocardium. Increasingly, visceral fat has been studied as a secondary immune organ, and EAT is no exception in this regard. Cellular subsets of EAT are associated with disease development. In heart failure (HF) patients, however, the immune characteristics of EAT have rarely been studied, especially those non-immune cells related to the immune microenvironment. Herein, an analysis of seven EAT samples by single-cell RNA sequencing (scRNA-Seq) is presented here, including 1 neonate, 1 infant, 1 child, 2 adults with heart failure (Adults-HF) and 2 adult heart transplant donors as non-heart failure control (Adults-Non HF). Analysis of 51730 high-quality cells revealed eleven major cell types in EAT. For the first time, the pseudo-temporal reconstruction technique was employed to plot the cell trajectories of various major cell types (such as T lymphocytes, fibroblasts, endothelial cells, monocytes, and smooth muscle cells) in EAT across different developmental stages, achieving a single-cell resolution. The dynamic gene expression patterns of major cell types presented the immune characteristics of metabolism disorder of zinc and copper ions, and downregulated immune-related pathways in EAT of adult patients with HF. These data provide insights regarding HF immune dysregulation at the cellular level.