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<p>Coronary atherosclerosis underlies life-threatening conditions such as myocardial infarction and stroke, yet its cellular dynamics remain incompletely understood. Here, through single-cell RNA sequencing of 27,941 cells from 56 human coronary segments, we constructed a disease-stage-resolved cellular atlas, revealing pathological remodelling of endothelial cells (ECs) into a progenitor-like state (EC5<sup><i>SLCO4A1</i>+</sup>) with low expression of canonical EC dysfunction signatures. EC5<sup><i>SLCO4A1</i>+</sup> abundance increased with atherosclerotic stage, and its emergence is driven by <i>PRDM15</i> through direct transcriptional activation. Analysis of the EC5<sup><i>SLCO4A1</i>+</sup> interaction network revealed extensive crosstalk with immune cell types, the interaction between which contributed to atherosclerotic progression. Endothelial overexpression of <i>Prdm15</i> in vivo exacerbated atherosclerosis, while its suppression ameliorated the disease phenotype, with diminished EC5<sup><i>SLCO4A1</i>+</sup>-like cells and immune infiltration. Our findings underscore the central role of EC subtype remodelling in the progression of human coronary atherosclerosis and reveal tractable targets for therapeutic intervention.</p>

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Single-cell transcriptomics uncovers endothelial progenitor-like remodelling driving human coronary atherosclerosis progression

  • 期刊论文

  • 发表日期：

    2026年7月14日

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  • Fang Yao,
  • Fangzhou Li,
  • Shujie Gai,
  • Yinan Chen,
  • Fei Liu,
  • Xingzhong Zhang,
  • Jun Li,
  • Lin Mao,
  • Liliang Guo,
  • Kun Xing,
  • Juan Huang,
  • Shufang Fu,
  • Yang Sun,
  • Jinhua Chen,
  • Heng Zhang,
  • Yihan Chen,
  • Bingying Zhou,
  • Li Wang,
  • Zhe Zheng

摘要

Coronary atherosclerosis underlies life-threatening conditions such as myocardial infarction and stroke, yet its cellular dynamics remain incompletely understood. Here, through single-cell RNA sequencing of 27,941 cells from 56 human coronary segments, we constructed a disease-stage-resolved cellular atlas, revealing pathological remodelling of endothelial cells (ECs) into a progenitor-like state (EC5SLCO4A1+) with low expression of canonical EC dysfunction signatures. EC5SLCO4A1+ abundance increased with atherosclerotic stage, and its emergence is driven by PRDM15 through direct transcriptional activation. Analysis of the EC5SLCO4A1+ interaction network revealed extensive crosstalk with immune cell types, the interaction between which contributed to atherosclerotic progression. Endothelial overexpression of Prdm15 in vivo exacerbated atherosclerosis, while its suppression ameliorated the disease phenotype, with diminished EC5SLCO4A1+-like cells and immune infiltration. Our findings underscore the central role of EC subtype remodelling in the progression of human coronary atherosclerosis and reveal tractable targets for therapeutic intervention.