Single-Cell RNA Sequencing of the Cardiovascular System: New Looks for Old Diseases

Abstract

Cardiovascular disease encompasses a wide range of conditions, resulting in the highest number of deaths worldwide. The underlying pathologies surrounding cardiovascular disease include a vast and complicated network of both cellular and molecular mechanisms. Unique phenotypic alterations in specific cell types, visualized as varying RNA expression-levels (both coding and non-coding), have been identified as crucial factors in the pathology underlying conditions such as heart failure and atherosclerosis. Recent advances in single-cell RNA sequencing (scRNA-seq) have elucidated a new realm of cell subpopulations and transcriptional variations that are associated with normal and pathological physiology in a wide variety of diseases. This breakthrough in the phenotypical understanding of our cells has brought novel insight into cardiovascular basic science. scRNA-seq allows for separation of widely distinct cell subpopulations which were, until recently, simply averaged together with bulk-tissue RNA-seq. scRNA-seq has been used to identify novel cell types in the heart and vasculature that could be implicated in a variety of disease pathologies. Furthermore, scRNA-seq has been able to identify significant heterogeneity of phenotypes within individual cell subtype populations. The ability to characterize single cells based on transcriptional phenotypes allows researchers the ability to map development of cells and identify changes in specific subpopulations due to diseases at a very high throughput. This review looks at recent scRNA-seq studies of various aspects of the cardiovascular system and discusses their potential value to our understanding of the cardiovascular system and pathology.

Integration of multiple imaging platforms to uncover cardiac defects in adult zebrafish

“…Regarding other cardiac compartments, the extent of retrograde flow across the AVC was associated with a smaller ventricle and bigger atrium, consistent with the consequences of valve regurgitation which leads to a higher amount of blood stalling in the atrium (Chaudhry et al, 2019). Interestingly, mutants -but not WT -with a higher regurgitation fraction in the OFT also displayed higher regurgitation fraction in the AVC, suggesting that these defects are closely associated.…”

Expression of Calcification and Extracellular Matrix Genes in the Cardiovascular System of the Healthy Domestic Sheep (Ovis aries)

“…Here we have built a foundation to explore the transcriptome of the developing and aging cardiovascular system and provided a highly useful comprehensive resource. Recent advances in single cell RNA-seq technology provide a new frontier to understand cell type specific gene expression and will allow us to further de-convolute expression patterns in cardiovascular tissues (Chaudhry et al, 2019). Further in-depth studies will be necessary to understand the gene expression networks and molecular pathways that exist in the different cardiovascular structures, and how they develop and change as the cardiovascular system matures.…”

Big Data Approaches in Heart Failure Research

“…Single-cell RNAseq has already been applied to study the cardiovascular system (reviewed in [77][78][79][80]). To date, studies have focused on the description of cardiac cell lineage heterogeneity and trajectory in mice [79,[81][82][83], as well as on human cardiogenesis [84][85][86][87][88].…”