New perspectives of the cardiac cellular landscape: mapping cellular mediators of cardiac fibrosis using single-cell transcriptomics

Abstract

Single-cell transcriptomics enables inference of context-dependent phenotypes of individual cells and determination of cellular diversity of complex tissues. Cardiac fibrosis is a leading factor in the development of heart failure and a major cause of morbidity and mortality worldwide with no effective treatment. Single-cell RNA-sequencing (scRNA-seq) offers a promising new platform to identify new cellular and molecular protagonists that may drive cardiac fibrosis and development of heart failure. This review will summarize the application scRNA-seq for understanding cardiac fibrosis and development of heart failure. We will also discuss some key considerations in interpreting scRNA-seq data and some of its limitations.

Diastolic dysfunction in a pre-clinical model of diabetes is associated with changes in the cardiac non-myocyte cellular composition

“…However, in these contexts, fibroblast gene expression and phenotype are distinct [ 22 ]. For example, in myocardial infarction (MI), fibroblasts rapidly differentiate into activated fibroblasts and myofibroblasts—both well-established drivers of cardiac ECM deposition [ 23 ]. Conversely, we have recently reported that myofibroblasts are absent during the development of chronic fibrosis in angiotensin II-induced cardiac remodelling [ 14 ].…”

Epigenetic Repression of Chloride Channel Accessory 2 Transcription in Cardiac Fibroblast: Implication in Cardiac Fibrosis

“…(K) A schematic model. (Krstevski et al, 2020). We show here that Twist1 is responsible for Clca2 trans-repression in activated cardiac fibroblasts by directly binding to the E-box element located on the Clca2 promoter (Figure 5K).…”

“…Recent investigations have provided irrefutable evidence to support resident fibroblasts as the primary source of myofibroblasts contributing to cardiac fibrosis ( Travers et al, 2016 ). Dynamic transcriptomic changes highlight the transition from quiescent cardiac fibroblasts to mature myofibroblasts ( Krstevski et al, 2020 ). We show here that Twist1 is responsible for Clca2 trans- repression in activated cardiac fibroblasts by directly binding to the E-box element located on the Clca2 promoter ( Figure 5K ).…”

Diastolic Dysfunction in a Pre-clinical Model of Diabetes Is Associated With Changes in the Cardiac Non-myocyte Cellular Composition

“…Numerous studies have implicated cardiac broblasts in diabetic cardiomyopathy, however their precise role in diabetes in vivo is still unknown. Cardiac broblasts are the primary cell type involved in deposition of extracellular matrix (ECM) in both states of acute injury or chronic stress [21]. However, in these contexts, broblast gene expression and phenotype are distinct [13].…”