Systematic analysis and exploration of single-cell transcriptomes in aortic aneurysm

doi:10.3969/j.issn.1674-8115.2025.06.008

Abstract

Abstract:

Objective ·To explore the single-cell landscape of aortic aneurysm (AA) utilizing single-cell RNA sequencing (scRNA-seq) technology. Methods ·A systematic search of the Gene Expression Omnibus (GEO) was conducted to collect all datasets meeting the inclusion criteria. Changes in the percentage of cellular composition of AA tissues versus normal control tissues were analyzed using R language and the Seurat package. Cell-cell interactions were assessed by gene expression levels of cellular receptor-ligand pairs using the CellChat package. Cellular senescence was scored and compared based on the SenMayo Senescence gene set using the AUCell package.Single-cell transcriptional data were simulated as traditional transcriptome data for differential gene screening and gene pathway enrichment analysis of pericytes. Results ·A total of nine datasets meeting the criteria were included. After quality control and merging, RNA count data for 104 570 cells were obtained, comprising 48 311 in the control group and 56 259 in the AA group. Cells were categorized into 19 clusters and annotated into 14 cell types. Compared with the control group, the proportion of pericytes in the AA group significantly decreased (P<0.001), while the proportions of monocytes/macrophages and dendritic cells increased (P=0.020, P=0.045). The number of intercellular interactions in the AA group was markedly higher than that in the control group; however, yet the interactions involving smooth muscle cells decreased, and the interaction intensity among pericytes diminished. There were 5 unique intercellular interactions in the control group and 13 unique interactions in the AA group, with the interaction involving SPP1 showing the highest relative information flow. Except for adipocytes, all cell types in the AA group exhibited significantly higher senescence scores (P<0.001), with an overall increase in the number of senescent cells (P<0.001), predominantly fibroblasts. Differential expression analysis of pericytes showed 185 upregulated genes and 151 downregulated genes in the AA group, with Spp1 exhibiting the highest upregulation. Pro-inflammatory pathways related to chemokine activity and CXC chemokine receptor binding were significantly enriched. Conclusion ·The cellular composition in AA tissues undergoes significant alterations, characterized by an increase in intercellular interactions and elevated levels of cellular senescence, with Spp1 identified as a key gene.

Key words: aortic aneurysm (AA), single-cell RNA sequencing (scRNA-seq), cell communication, cell senescence

CLC Number:

R543.1

ZHANG Xingyu, LI Ruogu. Systematic analysis and exploration of single-cell transcriptomes in aortic aneurysm[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2025, 45(6): 735-744.

Figures/Tables 8

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References 35

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Method for AA model establishment	Harvest time point/d	Sequencing platform	GSE number
ApoE knockout + angiotensin Ⅱ infusion	28	Illumina HiSeq 4000	GSE141732
ApoE knockout + angiotensin Ⅱ infusion	7	Illumina NovaSeq 6000	GSE233625
ApoE knockout + angiotensin Ⅱ infusion	28	Illumina NovaSeq 6000	GSE221789
ApoE knockout + angiotensin Ⅱ infusion	7	Illumina NovaSeq 6000	GSE213735
ApoE knockout + angiotensin Ⅱ infusion	28	Illumina HiSeq 4000	GSE141726
ApoE knockout + angiotensin Ⅱ infusion	28	Illumina HiSeq 4000	GSE186865
Paravascular CaCl₂ injection	4	Illumina NovaSeq 6000	GSE164678
Paravascular elastase injection	14	Illumina HiSeq 4000	GSE152583

Method for AA model establishment	Harvest time point/d	Sequencing platform	GSE number
ApoE knockout + angiotensin Ⅱ infusion	28	Illumina HiSeq 4000	GSE141732
ApoE knockout + angiotensin Ⅱ infusion	7	Illumina NovaSeq 6000	GSE233625
ApoE knockout + angiotensin Ⅱ infusion	28	Illumina NovaSeq 6000	GSE221789
ApoE knockout + angiotensin Ⅱ infusion	7	Illumina NovaSeq 6000	GSE213735
ApoE knockout + angiotensin Ⅱ infusion	28	Illumina HiSeq 4000	GSE141726
ApoE knockout + angiotensin Ⅱ infusion	28	Illumina HiSeq 4000	GSE186865
Paravascular CaCl₂ injection	4	Illumina NovaSeq 6000	GSE164678
Paravascular elastase injection	14	Illumina HiSeq 4000	GSE152583