Spatial transcriptomics in the human left atrial appendage and pulmonary vein sleeve

Area of Science:

• Cardiovascular Biology
• Genetics
• Molecular Biology

Background:

• Pulmonary vein (PV) isolation is crucial for atrial fibrillation (AF) ablation.
• Genetic risk loci for AF, like PITX2, are near genes involved in PV formation.
• Limited transcriptomic data exists for human PV tissues due to accessibility challenges.

Purpose of the Study:

• To perform spatial transcriptomic analysis on human PV and left atrial appendage (LAA) tissues.
• To identify cell types and gene expression patterns within PV and LAA.
• To investigate the role of AF-associated genes in PV and LAA.

Main Methods:

• Spatial transcriptomics on human PV and LAA tissues from unused transplant donors.
• Seurat clustering to identify distinct cell clusters.
• Analysis of cell-type specific marker genes and spatial gene expression patterns.

Main Results:

• Fifteen distinct cell clusters were identified, including cardiomyocytes, fibroblasts, vascular smooth muscle cells, endothelial cells, and adipocytes.
• Spatial transcriptomics resolved venous, cardiomyocyte, and epicardial regions in PVs, and fibrotic regions in LAA and PVs.
• AF-associated genes PITX2, SHOX2, and HCN4 were detected in both LAA and PVs, with SHOX2 showing higher expression in PVs.

Conclusions:

• Spatial transcriptomics is effective for analyzing human PV and LAA tissues.
• SHOX2 may play a significant regulatory role in pulmonary veins, potentially impacting atrial fibrillation.
• This study provides novel mechanistic insights into AF pathogenesis and PV biology.