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SnRNA-seq profiling of the ascending aorta and aortic arch from male and female Wnt1-Cre;Rosa26-mTmG mice

ABSTRACT: Vascular smooth muscle cells (VSMCs) in the ascending aorta and aortic arch arise from two distinct embryonic origins: the second heart field (SHF) and the cardiac neural crest (CNC). Whether these populations exhibit sex-dependent differences remains unknown. In this study, we generated Wnt1-Cre/Rosa26-mTmG lineage-tracing mice and performed single-nucleus RNA sequencing using the ascending aortae and aortic arch from both sexes. This study revealed the differential expression of VSMCs from different embryonic origin in both sexes.

ORGANISM(S): Mus musculus

PROVIDER: GSE329905 | GEO | 2026/05/15

REPOSITORIES: GEO

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Project description:Pathologies of large vessels, such as atherosclerosis and aneurysms tend to develop at specific sites in the vascular tree. The consistency with which these events emerge suggests that a combination of unique local stressors, particularly physical forces and disturbances in gene expression profiles underlies disease etiology. We sought to investigate whether transcriptional diversity in specific segments of the aorta could be used to identify emergence of site-restricted vascular disease. Transcriptional profiling was performed using single cell RNA-seq in the carotids, aortic arch, thoracic and abdominal aorta across both sexes. Analyses of the data identified sex-invariant region-specific differences that were further validated by immunocytochemistry. Analysis of vascular smooth muscle cell transcriptomics from distinct regions of the aorta and carotids showed a high degree of similarity, but also uncovered skewed expression of a small percentage of transcripts (7.2%) towards particular vascular segments (carotid, aortic arch, thoracic and abdominal aorta). In silico cross-reference of genes known to be associated with vascular disease with the unique transcriptional signatures validated our proposed hypothesis. Specifically, we found correlations between localized-diseased causing GWAS candidate genes and region-enriched signatures. Pair-wise comparison between anatomic regions across sexes identified regional sex-specific gene signatures highlighting prominent regional-sex dependent differences were observed in vSMCs of the thoracic and abdominal aorta, consistent with sex-specific burden of aneurysm in these regions. Of these regional sex-enriched candidates’, Mcam/CD146, showed ventral thoraco-abdominal distribution, enriched expression in females and it was significantly reduced in the AngII / hypercholesterolemic model of aortic aneurysm. Furthermore, induction of aneurysms in mice lacking Mcam/CD146 resulted in larger lesions and accelerated death due to dissection.

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SnRNA-seq profiling of the ascending aorta and aortic arch from male and female Wnt1-Cre;Rosa26-mTmG mice

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