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Large-scale Single-nuclei Profiling Identifies Role for ATRNL1 in Atrial Fibrillation [snRNA-seq]

ABSTRACT: Large-scale Single-nuclei Profiling Identifies Role for ATRNL1 in Atrial Fibrillation [snRNA-seq]

PROVIDER: PRJNA1075773 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27950900_1.fastq.gz	Fastqsanger.gz
	SRR27950900_2.fastq.gz	Fastqsanger.gz
	SRR27950901_1.fastq.gz	Fastqsanger.gz
	SRR27950901_2.fastq.gz	Fastqsanger.gz
	SRR27950902_1.fastq.gz	Fastqsanger.gz

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Large-scale Single-nuclei Profiling Identifies Role for ATRNL1 in Atrial Fibrillation [snRNA-seq]

Project description: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 performed single-nucleus RNA-seq (snRNA-seq) on age- and sex-matched left atrial (LA) samples from 18 patients with AF and 16 controls without AF. From more than 175,000 nuclei we identified 15 cell types but found that only cardiomyocytes (CMs) and macrophages (MΦs) had a significant number of differentially expressed genes in patients with AF. Attractin Like 1 (ATRNL1) was strongly overexpressed in CMs among patients with AF and localized to the intercalated discs. Further, in both knockdown and overexpression experiments in atrial human embryonic stem cell-derived CMs (hESC-aCMs) we identified a potent role for ATRNL1 in cell stress response, cardiac conduction, cell junction organization and in modulation of the cardiac action potential. Finally, we prioritized genes at the known genetic loci for AF and identified an unexpected expression for a leading AF candidate gene, KCNN3. In sum, we have identified a role for ATRNL1 and other differentially regulated genes that may serve as potential therapeutic targets for this common arrhythmia.

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Large-scale Single-nuclei Profiling Identifies Role for ATRNL1 in Atrial Fibrillation

Project description:Large-scale Single-nuclei Profiling Identifies Role for ATRNL1 in Atrial Fibrillation

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Project description:Analysis for early diagnosis of atrial fibrillation by finding changes in miRNA in the urine of patients with atrial fibrillation

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Project description:Large-scale Single-nuclei Profiling Identifies Role for ATRNL1 in Atrial Fibrillation [bulk RNA-seq]

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Project description:Regional differential expression of atrial fibrillation risk genes in the left atrium and pulmonary veins is not well studied, but may yield insights into atrial fibrillation pathogenesis. We tested the hypothesis that there is significant regional differential expression in left atrium structures. RNAseq was performed in 25 regions within the pulmonary veins (n=12), left atrial body (n=10), and left atrial appendage (n=3) from a 75 year old male with hypertension and atrial fibrillation who died of a stroke. These data show that genes involved in atrial fibrillation pathogenesis have substantial regional expression heterogeneity, particularly when comparing the left atrial body, pulmonary veins and left atrial appendage.

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