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Published on: September 20, 2024
A Multimodal Omics Framework to Empower Target Discovery for Cardiovascular Regeneration
Ziwen Li1, Mairi Brittan2, Nicholas L Mills2
1BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK. Ziwen.Cass.Li@ed.ac.uk.
Insights
Ischaemic heart disease poses a global health challenge. This review explores single-cell RNA sequencing (scRNA-seq) to find new targets for promoting heart regeneration and treating heart failure.
Area of Science:
- Cardiovascular Biology
- Regenerative Medicine
- Genomics
Background:
- Ischaemic heart disease (IHD) is a leading cause of morbidity and mortality worldwide.
- While revascularisation improves survival in acute myocardial infarction, limited cardiac regeneration and microvascular dysfunction contribute to heart failure.
- Novel therapeutic targets are needed to enhance myocardial repair and regeneration.
Purpose of the Study:
- To review current understanding of myocardial regeneration using single-cell RNA sequencing (scRNA-seq).
- To identify key mechanisms and cellular players involved in heart injury and repair across species and developmental stages.
- To propose a framework for discovering new therapeutic targets for cardiovascular regeneration.
Main Methods:
- Comprehensive review of studies utilizing scRNA-seq in healthy and injured hearts.
- Analysis of scRNA-seq data across multiple species and developmental stages.
- Synthesis of findings to propose a multi-species, multi-omics meta-analysis framework.
Main Results:
- scRNA-seq has provided high-resolution transcriptomic profiles of individual heart cells.
- Distinct cellular compositions and regenerative mechanisms have been identified in different cardiac regions and injury models.
- This technology has generated valuable single-cell atlases for various species.
Conclusions:
- scRNA-seq is a transformative technology for understanding cardiac regeneration.
- A multi-species, multi-omics approach can accelerate the discovery of novel targets for promoting cardiovascular regeneration.
- This strategy holds promise for developing new treatments for heart failure.
Abstract:
Ischaemic heart disease is a global healthcare challenge with high morbidity and mortality. Early revascularisation in acute myocardial infarction has improved survival; however, limited regenerative capacity and microvascular dysfunction often lead to impaired function and the development of heart failure. New mechanistic insights are required to identify robust targets for the development of novel strategies to promote regeneration. Single-cell RNA sequencing (scRNA-seq) has enabled profiling and analysis of the transcriptomes of individual cells at high resolution. Applications of scRNA-seq have generated single-cell atlases for multiple species, revealed distinct cellular compositions for different regions of the heart, and defined multiple mechanisms involved in myocardial injury-induced regeneration. In this review, we summarise findings from studies of healthy and injured hearts in multiple species and spanning different developmental stages. Based on this transformative technology, we propose a multi-species, multi-omics, meta-analysis framework to drive the discovery of new targets to promote cardiovascular regeneration.
