Single-cell Transcriptomic Atlas of Human Atrial Fibrillation

Abstract

Atrial fibrillation (AF) is becoming a significant public health challenge, presenting moderate treatment effects and a high recurrence rate. The lack of a complete, in-depth understanding of the pathogenesis of AF severely limits the capability of early diagnosis (and staging) and the development of mechanism-based, individual patient-targeted therapies. Using analyses of large-scale single-nucleus transcriptomes, we characterized the cell-type compositions of AF and non-AF atrial appendage tissues. We identified and validated disease-specific cardiac cell subpopulations of primary cell types, analyzed their co-expression gene modules, explored the differentiation of cell subclusters, and evaluated the intercellular communication signals among cell types and subclusters. Our data elucidate the disease-specific cardiac cell states, their enriched biological functions, and potential critical genes that might be markers or targets for novel interventions. Our study provides a comprehensive evaluation of the cellular composition of the AF atrium and reveals how the gene expression landscape is altered in human AF atrium tissue. Our study contributes to the understanding of AF formation and progression.