Abstract
Atherosclerotic carotid stenosis is a major cause of stroke, yet the mechanisms driving plaque instability remain incompletely understood. Perivascular adipose tissue (PVAT), the fat surrounding blood vessels, has been implicated in advanced atherosclerosis progression, but its cellular contributions are largely unknown. Here we show that PVAT contains two distinct adipose-derived stem cell (ADSC, multipotent progenitor cells within fat tissue) subsets. By analyzing 169 clinical samples using single-cell RNA sequencing and flow cytometry and pathological staining, we identify CD55⁺ADSCs as elevated in patients with symptomatic carotid stenosis or prior stroke. These cells migrate into plaques, differentiate into endothelial cells and promote pathological angiogenesis and vascular remodeling through FGF2 secretion thereby destabilising plaques. A second population, CXCL14+ADSCs exacerbate inflammation by recruiting immune cells via the CXCL12-CXCR4 axis. Our findings identify perivascular CD55+ADSCs as a therapeutic target for atherosclerosis management.
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Acknowledgements
The authors would like to thank Professor Chen Yan for her guidance on the article structure and experimental design; SHBIO and BGI for assistance with single-cell sequencing; Dr. Lili Li and Dr. Jie Kong from State Key Laboratory of Common Mechanism Research of Major Diseases for assistance with confocal imaging and in vivo bioluminescence imaging; Dr. Jiahuan Chen and Dr. Xiaolin Liu from State Key Laboratory of Common Mechanism Research of Major Diseases for assistance with cell sorting; Mr. Jianting Li and Ms. Sumei Li from Beijing Mybiosciences for assistance with full spectrum flow cytometry; and Dr. Junling Pang and Dr. Bolun Li for assistance with manuscript editing. This study received funding from the National Natural Science Foundation of China (No. 82470516 for B.L., No. 62503501 for K.L., No. 82502441 for Z.X., No. 82070498 for B.L. and No. 82100521 for Z.L.1[Zhichao Lai]), the Natural Science Foundation of Beijing Municipality (No. L248071 for B.L.), the Fundamental Research Funds for the Central Universities (No. 332024150 for J.C., No. 3332025010 for Z.X. and 3332025111 for Y.F.), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (No. 2022-JKCS-09 for B.L. and No. 2022-I2M-C&T-A-002 for B.L.), the National High Level Hospital Clinical Research Funding (2025-PUMCH-D-001 for B.L., 2025-PUMCH-A-181 for K.L., 2025-PUMCH-A-179 for Z.L.1 and 2022-PUMCH-B-125 for B.L.) and the National College Student’s Innovation Training Program (No. 2025dcxm176 for Y.L.).
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Y.H. and X.Z. are employees of Beijing Geneworks Technology Co., Ltd. The other authors declare no competing interests.
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Chen, J., Li, K., Shao, J. et al. Perivascular adipose single-cell atlas identifies CD55+ adipose-derived stem cells as vascular remodeling regulators in atherosclerosis. Nat Commun (2026). https://doi.org/10.1038/s41467-026-72962-z
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DOI: https://doi.org/10.1038/s41467-026-72962-z
