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

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

doi:10.1038/s41467-024-54296-w

Nature Communications (Nov 2024)

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

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

Affiliations

Matthew C. Hill: Cardiovascular Disease Initiative & Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard
Bridget Simonson: Cardiovascular Disease Initiative & Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard
Carolina Roselli: Cardiovascular Disease Initiative & Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard
Ling Xiao: Cardiovascular Disease Initiative & Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard
Caroline N. Herndon: Cardiovascular Disease Initiative & Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard
Mark Chaffin: Cardiovascular Disease Initiative & Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard
Helene Mantineo: Cardiovascular Disease Initiative & Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard
Ondine Atwa: Cardiovascular Disease Initiative & Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard
Harshit Bhasin: Cardiovascular Disease Initiative & Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard
Yasmine Guedira: Cardiovascular Disease Initiative & Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard
Kenneth C. Bedi: Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania
Kenneth B. Margulies: Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania
Carla A. Klattenhoff: Precision Cardiology Laboratory, Bayer US, LLC
Nathan R. Tucker: Departments of Pharmacology and Medicine, SUNY Upstate Medical University
Patrick T. Ellinor: Cardiovascular Disease Initiative & Precision Cardiology Laboratory, The Broad Institute of MIT and Harvard

DOI: https://doi.org/10.1038/s41467-024-54296-w
Journal volume & issue: Vol. 15, no. 1
pp. 1 – 16

Abstract

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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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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