Single-Cell Transcriptomics Reveals the Difference of Aortic Atherosclerosis Response to Phytosterols and Oxidation Products of Sterols

文献类型： 外文期刊

第一作者： Wang, Zhangtie

作者： Wang, Zhangtie;Wang, Mengmeng;Xiao, Fan;Liu, Yan;Lu, Baiyi;Lu, Yunrui;Ji, Yongli;Xie, Yao;Simal-Gandara, Jesus;Battino, Maurizio;Xiao, Jianbo;Zhang, Liangxiao;Li, Peiwu;Lu, Baiyi

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关键词： atherosclerosis; fibroblasts; phytosterols; sterol oxidation products; single-cell RNA sequence

期刊名称：MOLECULAR NUTRITION & FOOD RESEARCH （ 影响因子：5.2； 五年影响因子：6.2 ）

ISSN： 1613-4125

年卷期： 2023 年 67 卷 12 期

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收录情况： SCI

摘要： ScopePhytosterols (PS) and sterol oxidation products are key dietary factors influencing atherosclerosis besides cholesterol, although the mechanisms remain elusive. Recently, single-cell RNA sequencing (scRNA-seq) has revealed the heterogeneity of multiple cell types associated with complex pathogenesis in atherosclerosis development. Methods and resultsHere, scRNA-seq is performed to investigate the alterations in the aortic cells from ApoE(-/-) mice induced by diet-derived PS or two sterol oxidation products, phytosterols oxidation products (POPs), and cholesterol oxidation products (COPs). The study identifies four fibroblast subpopulations with different functions, and immunofluorescence demonstrates their spatial heterogeneity, providing evidence that suggests the transformation of smooth muscle cells (SMCs) and fibroblasts in atherosclerosis. The composition and gene expression profiles of aortic cells change broadly in response to PS/COPs/POPs exposure. Notably, PS exhibits an atheroprotective effect where different gene expressions are mainly found in B cells. Exposure to COPs accelerates atherosclerosis and results in marked alternations in myofibroblast subpopulations and T cells, while POPs only alter fibroblast subpopulations and B cells. ConclusionThe data elucidate the effects of dietary PS/COPs/POPs on aortic cells during atherosclerosis development, especially on the newly identified fibroblast subpopulations.

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