ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1638083
This article is part of the Research TopicExploring Cardiovascular and Cerebrovascular Diseases Interaction with Inflammation: Biomarkers, Drug Targets, and Personalized Treatments through Multi-omics Data Integration, Volume IIView all 5 articles
Single-cell RNA Sequencing Analysis Reveals the Critical Role of Fibroblasts in Aortic Progeria-associated Vascular Remodeling in Hutchinson-Gilford Progeria Syndrome Mice
Provisionally accepted
- 1Department of Dermatology, China-Japan Union Hospital, Jilin University, Changchun, China
- 2Department of Biobank, China-Japan Union Hospital, Jilin University, Changchun, China
- 3Phase I Clinical Trial Laboratory, China-Japan Union Hospital, Jilin University, Changchun, China
- 4Institute of Antler Science and Product Technology, Changchun Sci-Tech University, Changchun, China
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Patients with Hutchinson-Gilford progeria syndrome (HGPS) typically succumb to cardiovascular diseases in their teens. Although fibroblasts have been implicated in the progression of arteriosclerosis, their roles and mechanisms in progeroid aorta remain poorly understood. In this study, we characterized the aortic tissues of HGPS mice using single-cell RNA sequencing, with a focus on fibroblasts. Fibroblasts exhibited altered gene expression profiles associated with extracellular matrix dysregulation and inflammatory modulation, along with elevated senescence-associated secretory phenotype (SASP) scores in HGPS mice. Fibroblasts demonstrated the highest interaction frequency and intensity among aortic cell populations, with the strongest intercellular crosstalk observed between fibroblasts and dysfunctional vascular smooth muscle cells. We defined nine fibroblast subclusters and delineated their distinct transcriptional signatures, developmental trajectories, and interaction networks. Additionally, we identified significant upregulation of Lgals3bp in aortic fibroblasts of HGPS mice, which promoted the expression of pro-inflammatory factors and fibrosis-related genes. Collectively, our findings underscore the pivotal role of fibroblasts in aortic progeria-associated vascular remodeling in HGPS mice and suggest that Lgals3bp may represent a potential therapeutic target for aortic pathology in HGPS.
Keywords: HGPS, Fibroblasts, Single-cell transcriptome analysis, Aorta, Aging
Received: 30 May 2025; Accepted: 09 Oct 2025.
Copyright: © 2025 Sun, Yang, Zhou, Wu, Li, Hu and Cong. 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:
Qianying Hu, huqianying@jlu.edu.cn
Xianling Cong, congxl@jlu.edu.cn
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