Allelic Variation at 9p21.3 Orchestrates Widespread RNA Splicing Shifts Governing Vascular Smooth Muscle Cell Plasticity.

ABSTRACT: Genetic risk for coronary artery disease (CAD) has been linked to variants across more than 300 genomic loci. Among them, the 9p21.3 locus has the strongest and most consistent association with CAD, accounting for roughly 13% of cases. Despite its prominence, the mechanisms by which this locus influences vascular cells remain unclear. Here, we applied haplotype-biased genome editing in induced pluripotent stem cells (iPSCs), followed by differentiation into vascular smooth muscle cells (VSMCs), to compare the effects of the risk and non-risk 9p21.3 haplotypes within an identical genomic background. Using long-read RNA sequencing, we identified distinct allele-specific transcriptional programs driven by the two haplotypes. We unravel extensive reprogramming of mRNA splicing across the trans

SUBMITTER: Suryavanshi S 

PROVIDER: S-EPMC12871372 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature