COL10A1⁺ fibroblasts define rupture-prone abdominal aortic aneurysms and enable molecular risk stratification.
8 affiliations
- 1Department of Vascular Surgery, Xuzhou Central Hospital, Xuzhou, China.
- 2Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, China.
- 3Cancer Institute, Cellular Therapeutics School of Medicine, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China.
- 4Department of Vascular Surgery, Xuzhou Central Hospital, Xuzhou, China. [email protected].
- 5Xuzhou Clinical School of Xuzhou Medical University, Xuzhou, China. [email protected].
- 6Cancer Institute, Cellular Therapeutics School of Medicine, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China. [email protected].
- 7Center of Clinical Oncology, The Affiliated Hospital of Xuzhou Medical University, 99 West Huaihai Road, Xuzhou, Jiangsu, 221002, China. [email protected].
- 8Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China. [email protected].
Abstract
Background
Abdominal aortic aneurysm (AAA) rupture remains the leading cause of AAA-related mortality, while current clinical management relies primarily on aneurysm diameter, which inadequately predicts rupture risk. Increasing evidence suggests that stromal cell heterogeneity critically shapes vascular remodeling; however, the specific fibroblast states associated with AAA rupture predisposition remain poorly defined.Methods
We integrated cross-species single-cell RNA-sequencing datasets spanning the full spectrum of AAA progression to systematically characterize fibroblast heterogeneity and state transitions. Pseudotime trajectory analysis, transcriptional regulatory network inference, and ligand-receptor interaction modeling were applied to delineate fibroblast-associated microenvironmental programs. Based on these findings, a fibroblast-derived molecular signature was constructed and validated in an independent human AAA cohort.Results
Single-cell analysis revealed a progressive transition from homeostatic IGFBP6⁺ fibroblasts to a disease-associated COL10A1⁺ fibroblast state during AAA progression. COL10A1⁺ fibroblasts were selectively enriched in rupture-prone lesions and exhibited transcriptional programs linked to extracellular matrix remodeling and osteogenic-like activation. Intercellular communication analysis indicated that COL10A1⁺ fibroblasts were predicted to engage macrophage populations through coordinated ligand-receptor signaling pathways, including MDK, CSF1, and CXCL12, collectively delineating a rupture-associated vascular microenvironment. Translationally, leveraging this fibroblast state enabled the development of a minimal two-gene risk score (COL10A1-IGFBP6), which stratified AAA patients by molecular rupture risk independently of aneurysm diameter in the validation cohort.Conclusions
This study identifies a COL10A1⁺ fibroblast-associated transcriptional state that defines a rupture-prone vascular microenvironment in abdominal aortic aneurysm. The derived COL10A1-IGFBP6 signature establishes a biologically informed framework for molecular risk stratification, complementing anatomical size-based assessment and providing a foundation for future development of mechanism-guided strategies to refine AAA risk evaluation.
Related
- Immobilzation‐Induced Muscle Atrophy Exacerbates Vascular Calcification and Abdominal Aortic Aneurysms Through Irisin Downregulation
- Development of a nomogram for predicting wall irregular pulsation and risk stratification in intracranial aneurysms
- Neck geometry and shape compactness as additional haemodynamic modulators in abdominal aortic aneurysms
- Artificial intelligence-based surrogate modeling of hemodynamic indicators in abdominal aortic aneurysms using computational fluid dynamics
- A novel morphological assessment approach for abdominal aortic aneurysms: automated segmentation and measurement using a semi-supervised deep learning algorithm
BibTeX
@article{zhuo2026col10a1,
title = {{COL10A1⁺ fibroblasts define rupture-prone abdominal aortic aneurysms and enable molecular risk stratification.}},
author = {Huawei Zhuo and Chengxin Ou and Meng Duan and Jiwu Yang and Dan Liu},
journal = {Journal of translational medicine},
year = {2026},
month = jul,
doi = {10.1186/s12967-026-08689-8},
url = {https://europepmc.org/article/MED/42897652},
note = {CC BY},
}
RIS
TY - JOUR
TI - COL10A1⁺ fibroblasts define rupture-prone abdominal aortic aneurysms and enable molecular risk stratification.
AU - Huawei Zhuo
AU - Chengxin Ou
AU - Meng Duan
AU - Jiwu Yang
AU - Dan Liu
PY - 2026
DA - 2026/07/01
JO - Journal of translational medicine
DO - 10.1186/s12967-026-08689-8
UR - https://europepmc.org/article/MED/42897652
AB - Background Abdominal aortic aneurysm (AAA) rupture remains the leading cause of AAA-related mortality, while current clinical management relies primarily on aneurysm diameter, which inadequately predicts rupture risk. Increasing evidence suggests that stromal cell heterogeneity critically shapes vascular remodeling; however, the specific fibroblast states associated with AAA rupture predisposition remain poorly defined.Methods We integrated cross-species single-cell RNA-sequencing datasets spanning the full spectrum of AAA progression to systematically characterize fibroblast heterogeneity and state transitions. Pseudotime trajectory analysis, transcriptional regulatory network inference, and ligand-receptor interaction modeling were applied to delineate fibroblast-associated microenvironmental programs. Based on these findings, a fibroblast-derived molecular signature was constructed and validated in an independent human AAA cohort.Results Single-cell analysis revealed a progressive transition from homeostatic IGFBP6⁺ fibroblasts to a disease-associated COL10A1⁺ fibroblast state during AAA progression. COL10A1⁺ fibroblasts were selectively enriched in rupture-prone lesions and exhibited transcriptional programs linked to extracellular matrix remodeling and osteogenic-like activation. Intercellular communication analysis indicated that COL10A1⁺ fibroblasts were predicted to engage macrophage populations through coordinated ligand-receptor signaling pathways, including MDK, CSF1, and CXCL12, collectively delineating a rupture-associated vascular microenvironment. Translationally, leveraging this fibroblast state enabled the development of a minimal two-gene risk score (COL10A1-IGFBP6), which stratified AAA patients by molecular rupture risk independently of aneurysm diameter in the validation cohort.Conclusions This study identifies a COL10A1⁺ fibroblast-associated transcriptional state that defines a rupture-prone vascular microenvironment in abdominal aortic aneurysm. The derived COL10A1-IGFBP6 signature establishes a biologically informed framework for molecular risk stratification, complementing anatomical size-based assessment and providing a foundation for future development of mechanism-guided strategies to refine AAA risk evaluation.
SN - 1479-5876
ER -