Cited by 46Single-cell and spatial transcriptomicsAtherosclerosis and Cardiovascular DiseasesCardiovascular Health and Disease Prevention

Single-Cell RNA Sequencing and Assay for Transposase-Accessible Chromatin Using Sequencing Reveals Cellular and Molecular Dynamics of Aortic Aging in Mice

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Xie, Wenhui, Ke, Yilang, You, Qinyi, Li, Jing, Chen, Lu, Li, Dang, Fang, Jun, Chen, Xiaofeng +3 more·2022·Arteriosclerosis, Thrombosis, and Vascular Biology

Abstract

Objective: The impact of vascular aging on cardiovascular diseases has been extensively studied; however, little is known regarding the cellular and molecular mechanisms underlying age-related vascular aging in aortic cellular subpopulations. Approach and Results: Transcriptomes and transposase-accessible chromatin profiles from the aortas of 4-, 26-, and 86-week-old C57/BL6J mice were analyzed using single-cell RNA sequencing and assay for transposase-accessible chromatin sequencing. By integrating the heterogeneous transcriptome and chromatin accessibility data, we identified cell-specific TF (transcription factor) regulatory networks and open chromatin states. We also determined that aortic aging affects cell interactions, inflammation, cell type composition, dysregulation of transcriptional control, and chromatin accessibility. Endothelial cells 1 have higher gene set activity related to cellular senescence and aging than do endothelial cells 2. Moreover, construction of senescence trajectories shows that endothelial cell 1 and fibroblast senescence is associated with distinct TF open chromatin states and an mRNA expression model. Conclusions: Our data provide a system-wide model for transcriptional and epigenetic regulation during aortic aging at single-cell resolution.

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Crossref · 10.1161/atvbaha.121.316883

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Authors
Xie, W., Ke, Y., You, Q., Li, J., Chen, L., Li, D., Fang, J., Chen, X., Zhou, Y., Chen, L., & Hong, H.
Affiliations
  • Fujian Medical University (CN)
  • Union Hospital (CN)
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Published
2022-02
Volume
42
Issue
2
Pages
156-171
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
OpenAlex
W4200296738
Cited by
46
References
7
Citations by year
2026: 11 · 2025: 14 · 2024: 10 · 2023: 7 · 2022: 4
FWCI
1.65
Type
journal article
Language
en
Open access
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Natural Science Foundation of China (81570448, 82071560, 81800422)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
Keywords
aortic aging, vascular aging, endothelial cells, cellular senescence, chromatin accessibility, transcriptional regulatory networks, single-cell transcriptomics, fibroblasts, inflammation, epigenetic regulation
MeSH terms
Chromatin Immunoprecipitation Sequencing, Aging, Animals, Aorta, Cardiovascular Diseases, Chromatin, Mice, Inbred C57BL, Transcription Factors, Sequence Analysis, RNA, Transposases, Mice, Gene Regulatory Networks, Molecular Dynamics Simulation, Transcriptome

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