Large-scale single-nuclei profiling identifies role for ATRNL1 in atrial fibrillation

Year: 2024

Type: article

Abstract: Atrial fibrillation (AF) is the most common sustained arrhythmia in humans, yet the molecular basis of AF remains incompletely understood. To determine the cell type-specific transcriptional changes underlying AF, we perform single-nucleus RNA-seq (snRNA-seq) on left atrial (LA) samples from patients with AF and controls. From more than 175,000 nuclei we find that only cardiomyocytes (CMs) and macrophages (MΦs) have a significant number of differentially expressed genes in patients with AF. Attractin Like 1 (ATRNL1) was overexpressed in CMs among patients with AF and localized to the intercalated disks. Further, in both knockdown and overexpression experiments we identify a potent role for ATRNL1 in cell stress response, and in the modulation of the cardiac action potential. Finally, we detect an unexpected expression pattern for a leading AF candidate gene, KCNN3. In sum, we uncover a role for ATRNL1 which may serve as potential therapeutic target for this common arrhythmia. Characterizing atrial fibrillation (AF) at the single cell level is challenging. Here, the authors perform snRNA-seq on 18 patients with AF to investigate the cell composition, and gene expression shifts associated with this common arrhythmia.

Source: Nature Communications

DOI: 10.1038/s41467-024-54296-w

Authors: Matthew C. Hill, Bridget Simonson, Carolina Roselli, Ling Xiao, Caroline N. Herndon, Mark Chaffin, Helene Mantineo, Ondine Atwa, Harshit Bhasin, Yasmine Guedira, Kenneth C. Bedi, Kenneth B. Margulies, Carla A. Klattenhoff, Nathan R. Tucker, Patrick T. Ellinor

Institutions: Broad Institute, Massachusetts General Hospital, University of Pennsylvania, SUNY Upstate Medical University, Massachusetts Institute of Technology

Language: English

Topic: Cardiac electrophysiology and arrhythmias

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $6,790

Funders: American Heart Association, Massachusetts General Hospital, European Commission, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Institute on Drug Abuse, National Human Genome Research Institute, NIH Office of the Director, National Cancer Institute, National Institute of Neurological Disorders and Stroke, Common Fund

OpenAlex ID: W4404501626