Evidence mapPaperPMID 42007508Full record

ArticleClinical and translational medicine2026

Re-analysis of single-cell transcriptomics reveals a critical role of TNS1 gene in driving contractile VSMC transdifferentiation into macrophage-like SMC and atherosclerotic plaque instability.

Shuang Yang, Rui Fu, Xiaoxiao Ren, Mengyi Sun, Zhifan Li, Shufeng Chen, Bin Yang, Na Shi, Jue Ye, Chenyang Shen and 6 more

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Article in Clinical and translational medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

16 authors.

Shuang YangKey Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Rui FuKey Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xiaoxiao RenKey Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Mengyi SunKey Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Zhifan LiKey Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Shufeng ChenKey Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Bin YangKey Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Na ShiDepartment of Cardio-Metabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Jue YeState Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Chenyang ShenDepartment of Vascular Surgery, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xianqiang WangDepartment of Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Yongchun CuiBeijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Animal Experimental Center, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Naqiong WuDepartment of Cardio-Metabolic Medicine Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Xiangfeng LuKey Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.ORCID 0000-0003-4088-2338
Dongfeng GuKey Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Laiyuan WangKey Laboratory of Cardiovascular Epidemiology & Department of Epidemiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Funding

and National High Level Hospital Clinical Research Funding 2024-GSP-TJ-15National Natural Science Foundation of China 82030102National Natural Science Foundation of China 82170480National Natural Science Foundation of China 82570540the CAMS Innovation Fund for Medical Sciences 2021-I2M-1-008the CAMS Innovation Fund for Medical Sciences 2021-I2M-1-010
6 · The paper itself

Abstract

backgroundVascular smooth muscle cell (VSMC) phenotype switching plays a significant role in the pathogenesis of atherosclerosis (AS). However, the subtypes of VSMC transdifferentiation and their impact on AS progression and atherosclerotic plaque instability remains unclear.

methodsWe reanalysed scRNA-seq datasets of GSE155513 and GSE253903 and performed single-sample gene set enrichment analysis (ssGSEA) in three transcriptome datasets from unstable plaques to determine the major subtypes contributing the most to plaque instability. Using high-dimensional weighted gene co-expression network analysis (hdWGCNA), we identified hub genes in macrophage (MP)-like smooth muscle cells (SMCs) of unstable plaques. We conducted cell communication analysis according to tensin1 (TNS1) gene levels in VSMCs. TNS1 expression was analysed in human AS plaques. Finally, an AS model was established in VSMC-specific Tns1 knockout ApoE

resultsMP-like SMC was identified as the key subtype for plaque instability. hdWGCNA analysis for MP-like SMC identified blue module as the key gene module involved in unstable plaques. Decreased TNS1 expression in VSMCs was positively correlated with the down-regulation of contractile VSMC marker genes, SRF and MYCOD genes, negatively correlated with the up-regulation of CD68 and KLF4 genes, and activated VCAM, PDGF, THBS and CXCL signalling pathways. TNS1 mRNA expression levels were lower in human atherosclerotic arteries than in healthy arteries, and even lower in unstable plaques than in early and stable plaques. TNS1 protein levels in VSMCs were lower in human atherosclerotic plaques than in healthy arteries, and even lower in advanced plaques than in early plaques. VSMC-specific Tns1 gene deficiency aggravated AS progression and enhanced plaque instability with increased MP-like SMC transdifferentiation.

conclusionThe reduction of TNS1 gene in VSMCs might drive contractile VSMC transdifferentiation into MP-like SMC, the major subtype contributing to plaque instability. In vivo experimental results confirmed the role of Tns1 gene in contractile VSMC transdifferentiation into MP-like SMC and plaque instability.

Indexed as

Cell TransdifferentiationMacrophagesMuscle, Smooth, VascularMyocytes, Smooth MusclePlaque, AtheroscleroticTensinsTranscriptomeAnimalsHumansKruppel-Like Factor 4MiceSingle-Cell AnalysisKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4TensinsTNS1 protein, humanatherosclerotic plaque instabilitymacrophage (MP)‐like SMCsingle‐cell sequencing (scRNA‐seq) datasettensin1 (TNS1) geneVSMC transdifferentiation

Identifiers

PMID42007508
PMCPMC13093596

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.