Transcriptomics

Dataset Information

0

Single-cell and spatial transcriptomics uncovers the role of senescent vascular cells in pathological arterial remodeling during murine atherosclerosis


ABSTRACT: Studying cardiovascular senescence is crucial in understanding the diverse manifestations of disease-related changes in the cardiovascular system and their implications for overall health and disease. To systematically investigate the heterogeneity of senescent vascular cells in atherosclerosis, we employed the senescence reporter mouse p16TdTomato+/-, injected with an adeno-associated virus expressing PCSK9 to induce atherosclerosis when fed a high-fat diet (HFD). We then treated this mouse with the senolytic drug ABT-737 or vehicle. Whole-aorta single-cell RNA-sequencing (scRNA-seq) and Gene Set Enrichment Analysis (GSEA) using the SenMayo panel, uncovered 10 cell clusters displaying increased senescent features that were reduced by treatment with ABT-737. Interestingly, these clusters do not express ‘classical’ senescence markers such as p16 and p21, but were senescent based on SenMayo GSEA, indicating that the senescence transcriptomic signature in this niche requires deeper characterization. Using unbiased subclustering of the top four potentially senescent clusters, we identified subsets of cells increasing by HFD and reduced by ABT-737 treatment. Accordingly, unique transcripts associated with each subpopulation, such as Spp1, Ctsb, and Tnfrsf11b, implicated these cells in senescence-related signaling pathways. We then validated these findings by spatial transcriptomic profiling, locating senescent cells in the cap and core of brachiocephalic arteries from atherosclerotic mice. Our results uncover a new vascular-specific transcriptomic signature that may be exploited for therapeutic targeting in age-related vascular diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE239602 | GEO | 2024/07/28

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2018-11-20 | GSE115401 | GEO
2008-12-19 | GSE10003 | GEO
2021-02-17 | GSE128319 | GEO
2013-04-03 | E-GEOD-36938 | biostudies-arrayexpress
2013-04-03 | GSE36938 | GEO
2024-03-23 | GSE245935 | GEO
2024-06-24 | PXD053144 | Pride
2022-09-08 | PXD030955 | Pride
2017-04-18 | E-GEOD-77239 | biostudies-arrayexpress
2020-06-18 | GSE151475 | GEO