ArticleCirculation2025
Single-Cell Splicing Isoform Atlas of the Adult Human Heart and Heart Failure.
Article in Circulation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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Who cites it
11 citing papers in PubMed.
- A Spatiotemporal Single-Cell Atlas Uncovers Dysregulated ECM Dynamics and Septal Remodeling Arrest in Human Ventricular Septal Defects.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RNA splicing and cardiovascular disease: a guide for cardiologists.European heart journal · 2026Review
- Long-Read Single-Cell RNA Sequencing Reveals Dynamic Isoform Changes During Corneal Epithelial Wound Healing in Cynomolgus Monkeys.Investigative ophthalmology & visual science · 2026Article
- Integrated single-cell RNA sequencing and mendelian randomization analysis identifies causal immune-related driver genes in the heart failure inflammatory microenvironment.Cardiovascular diagnosis and therapy · 2026Article
- Proteogenomic analysis of the differential stability of cardiac protein isoforms.bioRxiv : the preprint server for biology · 2026Article
- The splice of life: an isoform-centric view of disease, technology, and therapeutics.The Journal of clinical investigation · 2026Review
- Transcriptome Reprogramming in Heart Failure: The Hidden Splicing Code.Current cardiology reports · 2026Review
- Allelic Variation at 9p21.3 Orchestrates Widespread RNA Splicing Shifts Governing Vascular Smooth Muscle Cell Plasticity.bioRxiv : the preprint server for biology · 2026Article
- Hypatia: Comparative Isoform Profiling Across Cell Populations from Long-Read Single-Cell Transcriptomes.bioRxiv : the preprint server for biology · 2026Article
- Long-Read Sequencing Reveals RNA Splicing Complexity in Human Diseases.Computational and structural biotechnology journal · 2026Review
- Review
Corrections and comments
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Authors and funding
18 authors.
Funding
Abstract
backgroundAlternative splicing plays crucial roles in normal heart development and cardiac disease by influencing protein-coding sequences, functional domains, and molecular networks. However, a detailed characterization of the human heart isoform landscape remains incomplete.
methodsLeveraging long-read single-nucleus RNA sequencing and computational analysis, we dissected full-length isoform heterogeneities, expression patterns, and usage shifts across cell types, cell states, and cardiac conditions of the adult left ventricle. We applied in silico approaches to assess the functional relevance of identified isoforms; validated isoform compositions of representative cardiac genes using reverse transcription quantitative polymerase chain reaction and targeted amplicon sequencing; and developed a web server for interactive navigation of our results.
resultsThe data revealed that isoform heterogeneity is widespread in the cardiac cellular system, serving as a posttranscriptional buffer mechanism that calibrates the molecule reservoirs in human hearts. In healthy left ventricles, ≈30% of cell type-specific genes were polyform, using multiple isoforms tailored to cell type-specific programs. Among ubiquitously expressed genes, >300 showed differential isoform usage with cell type specificity in normal hearts. Comparisons of cardiomyocytes across conditions uncovered 379 genes with marked isoform usage shifts, most of which are predicted to change protein coding outcomes through direct changes in protein coding sequences and switches between intron retention and non-protein-coding biotypes. In contrast, cell state-specific programs tend to operate on monoform genes associated with changes among cell states. In addition, our data revealed heart failure-associated differential isoform usage events in stromal and immune cell types in the cardiac microenvironment.
conclusionsWe present a comprehensive atlas of splicing isoforms in the normal adult heart and heart failure through long-read single-nucleus RNA sequencing and computational analyses. The results suggest crucial roles of isoforms in buffering core cellular programs and contributing to disease-associated cell states. The full-length details of these cell-specific isoforms serve as an important reference for downstream translational and mechanistic studies and are available on our online data portal at https://github.com/gaolabtools/heart-isoform-atlas.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.