ORIGINAL RESEARCH article
Front. Physiol.
Sec. Vascular Physiology
Single-cell transcriptomics reveals heterogeneous neutrophil populations and diagnostic biomarkers in atherosclerosis
Provisionally accepted
- 1Department of Nuclear Medicine, The 960th Hospital of the PLA, Jinan, China
- 2Medical Service Department, The 960th Hospital of the PLA, Jinan, China
- 3College of Liberal Arts & Sciences, University of Illinois Urbana-Champaign, Urbana, United States
- 4Jinzhou Medical University Graduate Training Base, The 960th Hospital of the PLA, Jinan, China
- 5Department of Pharmacy, The 960th Hospital of the PLA, Jinan, China
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Atherosclerosis, a chronic inflammatory arterial disease, involves complex interactions among diverse immune cells. Although single-cell RNA sequencing (scRNA-seq) has revealed cellular heterogeneity within atherosclerotic lesions, the diversity of neutrophils and their crucial genes in atherogenesis remain elusive. To address this, we integrated scRNA-seq data from six human atherosclerotic samples, encompassing 47,604 cells. Our analysis identified 16 distinct cell populations, highlighting an increased proportion of neutrophils in diseased arteries compared with healthy controls. Weighted gene co-expression network analysis (WGCNA) of neutrophil subtypes unveiled four key genes: CSTB, CHST15, RNASE1 and ATP2B1, which were validated as promising candidate biomarkers in independent cohorts (AUC>0.85). Elevated expression of these genes was further confirmed in the aortas of atherosclerotic mice and rats. Notably, these key genes correlated significantly with immune cell infiltration and were enriched in inflammatory response, ferroptosis, and atherosclerosis-related signaling pathways. Moreover, we predicted potential transcriptional regulators and therapeutic compounds targeting these genes. Collectively, our findings uncover the previously unrecognized heterogeneity of neutrophils in atherosclerosis and identify four key genes as promising diagnostic markers and therapeutic targets. These findings provide new insights into the pathogenesis of atherosclerosis and provide a theoretical basis for developing targeted therapies against this devastating disease.
Keywords: Atherosclerosis, biomarkers, immune cells, neutrophil subtypes, single-cell RNA sequencing
Received: 13 Sep 2025; Accepted: 28 Jan 2026.
Copyright: © 2026 Wang, Fu, Cai, Yang, Cui, Sun, Qiu, Ma and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xiaowen Ma
Min Li
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