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Updated: Oct 26, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Direct RNA sequencing-based multi-omics profiling reveals transcriptional and post-transcriptional remodeling in mice
Xin Liu1, Xueyu Han1,2, Wenjun Qiu1,2
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
Introduction:
Atherosclerosis is a vascular disease whose pathogenesis involves complex transcriptional and post-transcriptional regulation. Conventional bulk RNA-seq captures gene-level expression but does not fully resolve isoform diversity and RNA regulatory features.
Methods:
Male apolipoprotein E-deficient mice were fed normal chow (NC) or a Western diet (AS) for 16 weeks to establish diet-induced atherosclerosis. Aortic tissues were analyzed by direct RNA sequencing (DRS), bulk RNA-seq, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq). DRS data were used to reconstruct and quantify isoforms and to assess differential transcript expression, RNA modification, alternative splicing, alternative polyadenylation, and poly(A) tail length.
Results:
DRS generated a full-length aortic transcriptome comprising 35,587 transcripts, including 18,081 novel transcripts and 1,727 differentially expressed transcripts (DETs). Genes corresponding to known DETs were predominantly enriched in immune and inflammatory processes, whereas genes corresponding to novel DETs were primarily associated with lipid metabolism. Integration of ATAC-seq and DRS identified 13 DETs linked to altered chromatin accessibility. DRS further revealed extensive remodeling of RNA modifications, alternative splicing, and 3'-end processing, including dynamic changes in N6-methyladenosine, 5-methylcytosine, and adenosine-to-inosine. Additionally, 459 differential alternative splicing events and 1,320 differential polyadenylation sites were identified. A total of 613 genes exhibited altered 3'untranslated region length with coordinated shifts in poly(A) tail length.
Discussion:
By integrating DRS with bulk RNA-seq and ATAC-seq, this study establishes a multi-layered landscape of RNA transcriptional and post-transcriptional regulation in atherosclerosis. These findings provide a resource for future mechanistic investigations and for the development of RNA-targeted strategies in vascular disease.