ArticleJCI insight2022
Decoding the PITX2-controlled genetic network in atrial fibrillation.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Biomarker-based prediction of sinus rhythm in atrial fibrillation patients: the EAST-AFNET 4 biomolecule study.European heart journal · 2024Trial
- Article
- Chromatin topology control by a muscle-specific ribosomal protein.bioRxiv : the preprint server for biology · 2026Article
- Cardiac epigenome in heart development and disease.Nature reviews. Cardiology · 2026Review
- Cardiac conduction system malformations in heterotaxy result from dysregulated Pitx2 expression.JCI insight · 2026Article
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- Common Methylenetetrahydrofolate Reductase PolymorphismDiagnostics (Basel, Switzerland) · 2025Article
- Hypoxia Imaging as a Radiomics Signature in Tumors Using NovelbioRxiv : the preprint server for biology · 2025Article
- Single-Nucleotide Polymorphisms,International journal of molecular sciences · 2025Review
- Fibroblast-Restricted Inflammasome Activation Promotes Atrial Fibrillation and Heart Failure With Diastolic Dysfunction.JACC. Basic to translational science · 2025Article
- Dissecting cardiovascular disease-associated noncoding genetic variants using human iPSC models.Stem cell reports · 2025Review
- Bone morphogenetic protein 10, a rising star in the field of diabetes and cardiovascular disease.Journal of cellular and molecular medicine · 2024Review
- Single-Cell Atlas of Neonatal Mouse Hearts Reveals an Unexpected Cardiomyocyte.Journal of the American Heart Association · 2023Article
- Genetic Architecture of Ischaemic Strokes after COVID-19 Shows Similarities with Large Vessel Strokes.International journal of molecular sciences · 2023Article
- Connecting the Dots From GWAS to Function in Atrial Fibrillation forCirculation research · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Atrial fibrillation (AF), the most common sustained cardiac arrhythmia and a major risk factor for stroke, often arises through ectopic electrical impulses derived from the pulmonary veins (PVs). Sequence variants in enhancers controlling expression of the transcription factor PITX2, which is expressed in the cardiomyocytes (CMs) of the PV and left atrium (LA), have been implicated in AF predisposition. Single nuclei multiomic profiling of RNA and analysis of chromatin accessibility combined with spectral clustering uncovered distinct PV- and LA-enriched CM cell states. Pitx2-mutant PV and LA CMs exhibited gene expression changes consistent with cardiac dysfunction through cell type-distinct, PITX2-directed, cis-regulatory grammars controlling target gene expression. The perturbed network targets in each CM were enriched in distinct human AF predisposition genes, suggesting combinatorial risk for AF genesis. Our data further reveal that PV and LA Pitx2-mutant CMs signal to endothelial and endocardial cells through BMP10 signaling with pathogenic potential. This work provides a multiomic framework for interrogating the basis of AF predisposition in the PVs of humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.