Direct RNA sequencing-based multi-omics profiling reveals transcriptional and post-transcriptional remodeling in mice with diet-induced atherosclerosis.
4 affiliations
- 1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
- 2Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, China.
- 3Department of Vascular Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
- 4State Key Laboratory of Neurology and Oncology Drug Development, Nanjing, China.
Abstract
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.
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BibTeX
@article{liu2026direct,
title = {{Direct RNA sequencing-based multi-omics profiling reveals transcriptional and post-transcriptional remodeling in mice with diet-induced atherosclerosis.}},
author = {Xin Liu and Xueyu Han and Wenjun Qiu and Fengming Guo and Yan Guo and Yipeng Gao and Yuxin Liu and Ruichen Xu and Ke Hu and Bo Shen},
journal = {Frontiers in cell and developmental biology},
year = {2026},
month = oct,
doi = {10.3389/fcell.2026.1953461},
url = {https://europepmc.org/article/MED/42923067},
note = {CC BY},
}
RIS
TY - JOUR
TI - Direct RNA sequencing-based multi-omics profiling reveals transcriptional and post-transcriptional remodeling in mice with diet-induced atherosclerosis.
AU - Xin Liu
AU - Xueyu Han
AU - Wenjun Qiu
AU - Fengming Guo
AU - Yan Guo
AU - Yipeng Gao
AU - Yuxin Liu
AU - Ruichen Xu
AU - Ke Hu
AU - Bo Shen
PY - 2026
DA - 2026/10/08
JO - Frontiers in cell and developmental biology
DO - 10.3389/fcell.2026.1953461
UR - https://europepmc.org/article/MED/42923067
AB - 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.
SN - 2296-634X
ER -