ArticleCirculation. Genomic and precision medicine2025
Fibroblasts Are the Primary Contributors to a Disrupted Micro-Environment in End-Stage Pediatric Hypertrophic Cardiomyopathy.
Article in Circulation. Genomic and precision medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Single-Nuclei Transcriptomic Profiling of Human Myocardium in Long-Chain 3-Hydroxyacyl-Coenzyme A Dehydrogenase Deficiency.Circulation. Heart failure · 2026Article
- Single cell transcriptomic landscape of adult and pediatric non-ischemic cardiomyopathy.Journal of molecular and cellular cardiology · 2026Review
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Authors and funding
7 authors.
Funding
Abstract
backgroundHypertrophic cardiomyopathy (HCM) is a relatively rare but debilitating diagnosis in the pediatric population, and patients with end-stage HCM require heart transplantation. Here, we have examined the transcriptome in ventricular tissue from this patient group to identify cell states and underlying cellular processes unique to pediatric HCM.
methodsWe performed single-nucleus RNA sequencing (snRNA-seq) on explanted hearts at transplant in 3 pediatric patients with end-stage HCM and compared findings to pediatric control and adult HCM.
resultsWe identified distinct underlying cellular processes in cardiomyocytes, fibroblasts, endothelial cells, and myeloid cells compared with controls. Pediatric HCM was enriched in cardiomyocytes exhibiting stressed myocardium gene signatures and underlying pathways associated with cardiac hypertrophy; cardiac fibroblasts exhibited activation signatures and compared with adult patients, exhibited heightened downstream processes associated with fibrosis and a unique, myofibroblast-like cluster with increased metabolic stress and antiapoptotic properties. We noted depletion of tissue-resident macrophages and increased vascular remodeling in endothelial cells in pediatric HCM.
conclusionsOur analysis provides the first snRNA-seq analysis focused on end-stage pediatric HCM. Fibroblast-mediated cellular processes were the most prominent in pediatric HCM, which had more downstream processes associated with fibrosis than did adult HCM.
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