Single-Cell RNA Sequencing and Combinatorial Approaches for Understanding Heart Biology and Disease

Abstract

By directly measuring multiple molecular features in hundreds to millions of single cells, single-cell techniques allow for comprehensive characterization of the diversity of cells in the heart. These single-cell transcriptome and multi-omic studies are transforming our understanding of heart development and disease. Compared with single-dimensional inspections, the combination of transcriptomes with spatial dimensions and other omics can provide a comprehensive understanding of single-cell functions, microenvironment, dynamic processes, and their interrelationships. In this review, we will introduce the latest advances in cardiac health and disease at single-cell resolution; single-cell detection methods that can be used for transcriptome, genome, epigenome, and proteome analysis; single-cell multi-omics; as well as their future application prospects.

Keywords: heart development and disease; single-cell RNA sequencing; single-cell multi-omics.

Figure 1

Schematic representation of a commonly used application of single-cell sequencing (scRNA-seq) in the mammalian heart and single-cell transcriptome sequencing methodologies, including scRNA-seq, spatial transcriptome profiling, and multi-omic sequencing. The left panel represents heart development with arrows indicating the transition from embryonic to adult stages, with a focus on heart health. The right panel highlights cardiovascular disease stages, along with cutting-edge technologies such as single-cell RNA sequencing, spatial transcriptomics, and multi-omics approaches used to study the genome, proteins, DNA methylation, and chromatin accessibility.

Figure 2

Strategies for the integrated analysis of single-cell transcriptome and other single-cell omic approaches. Respective techniques are shown on the right. Single-cell multi-omic approaches are indicated with an asterisk (*). At present, scRNA-seq can be successfully combined with the analysis of the spatial distribution of RNA, the genome, chromatin accessibility, DNA methylation, and targeted protein expression.