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Here, we reanalyze bulk RNA-sequencing datasets from two studies (<jats:italic>N<\/jats:italic>\u2009=\u2009242) and identified 755 differentially expressed genes in left atrial appendages of individuals with persistent AF and non-AF controls. We combined the bulk RNA-sequencing differentially expressed genes with a left atrial appendage single-nucleus multi-omics dataset to assign genes to specific atrial cell types. We found noncoding genes at the <jats:italic>IFNG<\/jats:italic> locus (<jats:italic>LINC01479<\/jats:italic>, <jats:italic>IFNG-AS1<\/jats:italic>) strongly dysregulated in cardiomyocytes. We defined a gene expression signature potentially driven by androgen receptor signaling in cardiomyocytes from individuals with AF. Cell-type-specific gene expression modules suggested an increase in T cell and a decrease in adipocyte and neuronal cell gene expression in AF. Lastly, we showed that reducing NR4A1 expression, a marker of a poorly characterized human atrial fibroblast subtype, fibroblast activation markers, extracellular matrix remodeling and cell proliferation decreased.<\/jats:p>","DOI":"10.1038\/s44161-025-00626-0","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T21:39:00Z","timestamp":1742938740000},"page":"433-444","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Single-nucleus multi-omics implicates androgen receptor signaling in cardiomyocytes and NR4A1 regulation in fibroblasts during atrial fibrillation"],"prefix":"10.1038","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7619-3097","authenticated-orcid":false,"given":"Francis J. 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