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核心技术专利：CN118964589B侵权必究
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Single-cell RNA sequencing reveals sex differences in the subcellular composition and associated gene-regulatory network activity of human carotid plaques.

作者信息

Sukhavasi Katyayani, Mocci Giuseppe, Ma Lijiang, Hodonsky Chani J, Diez Benevante Ernest, Muhl Lars, Liu Jianping, Gustafsson Sonja, Buyandelger Byambajav, Koplev Simon, Lendahl Urban, Vanlandewijck Michael, Singha Prosanta, Örd Tiit, Beter Mustafa, Selvarajan Ilakya, Laakkonen Johanna P, Väli Marika, den Ruijter Hester M, Civelek Mete, Hao Ke, Ruusalepp Arno, Betsholtz Christer, Järve Heli, Kovacic Jason C, Miller Clint L, Romanoski Casey, Kaikkonen Minna U, Björkegren Johan L M

机构信息

Department of Cardiac Surgery and The Heart Clinic, Tartu University Hospital and Department of Cardiology, Institute of Clinical Medicine, Tartu University, Tartu, Estonia.

Department of Medicine, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge, Sweden.

出版信息

Nat Cardiovasc Res. 2025 Apr;4(4):412-432. doi: 10.1038/s44161-025-00628-y. Epub 2025 Apr 10.

DOI:10.1038/s44161-025-00628-y
PMID:40211055
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11994450/
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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/044418ef2e21/44161_2025_628_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/7cce249da2de/44161_2025_628_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/1d5545d7447c/44161_2025_628_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/ee87825c1f8a/44161_2025_628_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/3f879e8ee69b/44161_2025_628_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/23b96d124bd9/44161_2025_628_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/0a7229244446/44161_2025_628_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/f7c4bc3f7cb1/44161_2025_628_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/4e8677f87a13/44161_2025_628_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/627439f35945/44161_2025_628_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/8786a51b1823/44161_2025_628_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/e9cfbec436f9/44161_2025_628_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/c15519857b5e/44161_2025_628_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/1ddd87eb52eb/44161_2025_628_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/77c43a838cb9/44161_2025_628_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/9396fb50a6a0/44161_2025_628_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/044418ef2e21/44161_2025_628_Fig16_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/7cce249da2de/44161_2025_628_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/1d5545d7447c/44161_2025_628_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/ee87825c1f8a/44161_2025_628_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/3f879e8ee69b/44161_2025_628_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/23b96d124bd9/44161_2025_628_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/0a7229244446/44161_2025_628_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/f7c4bc3f7cb1/44161_2025_628_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/4e8677f87a13/44161_2025_628_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/627439f35945/44161_2025_628_Fig9_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/8786a51b1823/44161_2025_628_Fig10_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/e9cfbec436f9/44161_2025_628_Fig11_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/c15519857b5e/44161_2025_628_Fig12_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/1ddd87eb52eb/44161_2025_628_Fig13_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/77c43a838cb9/44161_2025_628_Fig14_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/9396fb50a6a0/44161_2025_628_Fig15_ESM.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a26a/11994450/044418ef2e21/44161_2025_628_Fig16_ESM.jpg

相似文献

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引用本文的文献

[1]
Development and validation of a machine learning model for predicting vulnerable carotid plaques using routine blood biomarkers and derived indicators: insights into sex-related risk patterns.

Cardiovasc Diabetol. 2025-8-10

[2]
Sex and the Garden of Eden.

Nat Cardiovasc Res. 2025-4

本文引用的文献

[1]
Single-Cell Gene-Regulatory Networks of Advanced Symptomatic Atherosclerosis.

Circ Res. 2024-5-24

[2]
Single-cell 'omic profiles of human aortic endothelial cells in vitro and human atherosclerotic lesions ex vivo reveal heterogeneity of endothelial subtype and response to activating perturbations.

Elife. 2024-4-5

[3]
Lipid-associated macrophages transition to an inflammatory state in human atherosclerosis increasing the risk of cerebrovascular complications.

Nat Cardiovasc Res. 2023-6-26

[4]
Multi-ancestry genetic analysis of gene regulation in coronary arteries prioritizes disease risk loci.

Cell Genom. 2024-1-10

[5]
Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis.

Cell Rep. 2023-11-28

[6]
Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques.

Arterioscler Thromb Vasc Biol. 2023-10

[7]
Optimizing the Cell Painting assay for image-based profiling.

Nat Protoc. 2023-7

[8]
The Gene Ontology knowledgebase in 2023.

Genetics. 2023-5-4

[9]
A mechanistic framework for cardiometabolic and coronary artery diseases.

Nat Cardiovasc Res. 2022-1

[10]
Endothelial-to-Mesenchymal Transition in Atherosclerosis: Friend or Foe?

Cells. 2022-9-21

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