Heart failure & cardiomyopathies

Single-Cell Splicing Isoform Atlas of the Adult Human Heart and Heart Failure

CirculationPublished Mechanistic study

Authors' conclusion

We 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.

Study context

Population
Adult human left ventricle, normal and HF
Comparison
Normal adult LV vs HF LV
Outcome
Isoform heterogeneity and usage
Methodological detailslong-read single-nucleus RNA sequencing, Validation by RT-qPCR and targeted amplicon sequencing, Interactive web server of results
  • Long-read single-nucleus RNA sequencing
  • Validation by RT-qPCR and targeted amplicon sequencing
  • Interactive web server of results

Main finding

As reported in the abstract

Cell type-specific genes in healthy LV that were polyform

≈30%

Ubiquitously expressed genes with cell type-specific differential isoform usage in normal hearts

>300

Genes with marked isoform usage shifts in cardiomyocytes across conditions, most predicted to change protein coding outcomes

379

Original publication

Single-Cell Splicing Isoform Atlas of the Adult Human Heart and Heart Failure. Circulation. Published 29 September 2025. doi:10.1161/circulationaha.125.074959

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