Sukhavasi, Katyayani and Mocci, Giuseppe and Ma, Lijiang and Hodonsky, Chani J. and Diez Benevante, Ernest and Muhl, Lars and Liu, Jianping and Gustafsson, Sonja and Buyandelger, Byambajav and Koplev, Simon and Lendahl, Urban and Vanlandewijck, Michael and Singha, Prosanta and Örd, Tiit and Beter, Mustafa and Selvarajan, Ilakya and Laakkonen, Johanna P. and Väli, Marika and den Ruijter, Hester M. and Civelek, Mete and Hao, Ke and Ruusalepp, Arno and Betsholtz, Christer and Järve, Heli and Kovacic, Jason C. and Miller, Clint L. and Romanoski, Casey and Kaikkonen, Minna U. and Björkegren, Johan L. M. (2025) Single-cell RNA sequencing reveals sex differences in the subcellular composition and associated gene-regulatory network activity of human carotid plaques. Nature Cardiovascular Research, 4 (4). pp.412-432. ISSN 2731-0590
Full text not available from this repository.Abstract
Abstract
Carotid stenosis causes ischemic stroke in both sexes, but the clinical presentation and plaque characteristics differ. Here we run deep single-cell sequencing of 7,690 human carotid plaque cells from male and female patients. While we found no sex differences in major cell types, we identified a predominance of the osteogenic phenotype in smooth muscle cells, immunomodulating macrophages (MPs) and endothelial cells (ECs) undergoing endothelial-to-mesenchymal transition in females. In males, we found smooth muscle cells with the chondrocytic phenotype, MPs involved in tissue remodeling and ECs with angiogenic activity. Sex-biased subcellular clusters were integrated with tissue-specific gene-regulatory networks (GRNs) from the Stockholm–Tartu Atherosclerosis Reverse Network Engineering Task study. We identified GRN195 involved in angiogenesis and T cell-mediated cytotoxicity in male ECs, while in females, we found GRN33 and GRN122 related to TREM2 − /TREM1 + MPs and endothelial-to-mesenchymal transition. The impact of GRN195 on EC proliferation in males was functionally validated, providing evidence for potential therapy targets for atherosclerosis that are sex specific.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 05 May 2025 06:55 |
| Last Modified: | 05 May 2025 06:55 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1699 |
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