GEO series
Spatial transcriptomic profiling of the human aortic valve reveals cellular sex differences near sites of calcification
GSE306288
Homo sapiens
Other; Expression profiling by high throughput sequencing
17 samples
Submitted 2026/06/03
Platform GPL24676
Summary
Sex differences in aortic valve stenosis (AVS) progression have been documented clinically, but the underlying cellular mechanisms that drive sex-dependent calcification in aortic valve tissue remain poorly understood. Here, we harnessed single cell and spatial transcriptomics to investigate mechanisms that drive sex dependent spatial organization of valvular interstitial cell (VIC) and macrophage gene expression near calcification sites in human male and female aortic valve tissue. Histological analyses of aortic valve tissues stratified into healthy and diseased cohorts based on degree of calcification reveal increased valve calcification area in diseased male aortic valves relative to female, and increased valve thickening in diseased female aortic valves. Single cell sequencing analysis of heterogeneous valvular interstitial cell (VIC) populations reveals male-dependent gene expression of the Activator Protein 1 (AP-1) transcription factor complex. Spatial transcriptomics and RNA-FISH analyses of VIC populations near sites of calcification revealed male-dependent gene expression localization of Cartilage Oligomeric Matrix Protein (COMP), as opposed to diffuse COMP expression in female VICs. Cell-cell communication analyses were used to determine female-specific macrophage-VIC interactions. Secreted phosphoprotein 1 (also known as osteopontin) expressed from macrophages interacts with the cell surface receptor CD44 expressed by VICs to drive a pro-fibrotic phenotype in female aortic valves. Together, our results reveal sex differences in VIC and macrophage heterogeneity and functions near sites of calcification in aortic valve tissue. Our results highlight the importance of sex-based transcriptomics analyses to understand the cellular phenotypes responsible for causing sex differences in aortic valve fibrosis calcification.
Published in
Baddour T, Ninh VK, Gorashi RM et al.
· Arteriosclerosis, thrombosis, and vascular biology 2026
· PMID 42206364
· doi:10.1161/ATVBAHA.126.324694
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE306288_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 17 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1310428 and SRA study SRP612249. Searching any of these in the dataset finder brings you back here.
Study design
17 conditions, each sampled once — no replicated groups
Read from 17 sample titles: 17 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
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- GSM9196841 patient 1 human aortic valve leaflet cells, male, diseased
- GSM9196842 patient 2 human aortic valve leaflet cells, male, healthy
- GSM9196843 patient 5 human aortic valve leaflet cells, male, diseased
- GSM9196844 patient 10 human aortic valve leaflet cells, male, healthy
- GSM9196845 patient 22 human aortic valve leaflet cells, male, healthy
- GSM9196846 patient 1A human aortic valve leaflet tissue, male, diseased
- GSM9196847 patient 1B human aortic valve leaflet tissue, male, diseased
- GSM9196848 patient 6A human aortic valve leaflet tissue, female, diseased
- GSM9196849 patient 6B human aortic valve leaflet tissue, female, diseased
- GSM9759905 patient 15 human aortic valve leaflet cells, male, diseased
- GSM9759906 patient 21 human aortic valve leaflet cells, female, diseased
- GSM9759907 patient 23 human aortic valve leaflet cells, female, diseased
- GSM9759908 patient 27 human aortic valve leaflet cells, female, diseased
- GSM9759909 patient 18V human aortic valve leaflet tissue, female, diseased
- GSM9759910 patient 20V human aortic valve leaflet tissue, male, diseased
- GSM9759911 patient 23V human aortic valve leaflet tissue, female, diseased
- GSM9759912 patient 29V human aortic valve leaflet tissue, male, diseased
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