Single-cell RNA sequencing reveals cardiac fibroblast-specific transcriptomic changes in dilated cardiomyopathy

Adam Russell-Hallinan, Oisín Cappa, Lauren Kerrigan*, Claire Tonry, Kevin Edgar, Nadezhda Glezeva, Mark Ledwidge, Kenneth McDonald, Patrick Collier, David A. Simpson, Chris J. Watson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Abstract

Dilated cardiomyopathy (DCM) is the most common cause of heart failure, with a complex aetiology involving multiple cell types. We aimed to detect cell-specific transcriptomic alterations in DCM through analysis that leveraged recent advancements in single-cell analytical tools. Single-cell RNA sequencing (scRNA-seq) data from human DCM cardiac tissue were subjected to an updated bioinformatic workflow in which unsupervised clustering was paired with reference label transfer to more comprehensively annotate the dataset. Differential gene expression was detected primarily in the cardiac fibroblast population. Bulk RNA sequencing was performed on an independent cohort of human cardiac tissue and compared with scRNA-seq gene alterations to generate a stratified list of higher-confidence, fibroblast-specific expression candidates for further validation. Concordant gene dysregulation was confirmed in TGFβ-induced fibroblasts. Functional assessment of gene candidates showed that AEBP1 may play a significant role in fibroblast activation. This unbiased approach enabled improved resolution of cardiac cell-type-specific transcriptomic alterations in DCM.

Original languageEnglish
Article number752
Number of pages14
JournalCells
Volume13
Issue number9
Early online date26 Apr 2024
DOIs
Publication statusPublished - May 2024

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