A single-cell atlas of intracranial aneurysm progression identifies a dysfunctional VSMC subpopulation associated with rupture risk.
- 1Department of Neurosurgery, Ankang Hospital of Traditional Chinese Medicine, Ankang, Shaanxi Province, China. [email protected].
- 2Department of Neurosurgery, Ankang Hospital of Traditional Chinese Medicine, Ankang, Shaanxi Province, China.
Abstract
Background
Intracranial aneurysm (IA) rupture is a life-threatening event. While inflammation is implicated, the cellular mechanisms associated with progression from stable lesion to rupture remain poorly defined at single-cell resolution.Methods
We performed single-cell RNA sequencing (scRNA-seq) on a mouse model spanning sham, formed, and ruptured IA stages. Computational analyses included trajectory inference, cell-cell communication analysis, and metabolic scoring. Key findings were validated using human IA bulk RNA-seq data and protein-level assays on matched clinical tissues.Results
Our single-cell atlas revealed a progressive "inflammatory-lytic" microenvironment marked by immune cell infiltration and vascular smooth muscle cell (VSMC) depletion. We identified a metabolically specialized VSMC subpopulation (VSMC_0) that was selectively lost in formed and ruptured aneurysms. Pseudotime analysis indicated VSMC differentiation blockade, associated with downregulation of the structural genes actin alpha2, smooth muscle (ACTA2) and prolyl 4-hydroxylase subunit alpha2 (P4HA2), which correlated with irregular aneurysm shape a strong clinical predictor of rupture risk. Cell communication analysis positioned VSMC_0 as a signaling hub to macrophages, suggesting a feed-forward inflammatory loop. These findings were validated in human IAs tissues.Conclusion
Our study identifies VSMC phenotypic dysregulation as a key correlate of IA instability, linking molecular deficits to clinical rupture predictors. This reframes IA as a disorder of vascular cellular identity and communication, revealing potential therapeutic targets for aneurysm stabilization.
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BibTeX
@article{chen2026singlecell,
title = {{A single-cell atlas of intracranial aneurysm progression identifies a dysfunctional VSMC subpopulation associated with rupture risk.}},
author = {Xiangrong Chen and Bikun Liu and Xiaofeng Zhou and Zongtao Wu and Dongze Xu and Jingcheng Zhan and Jinliang Liu and Mao Ling and Fan Liu},
journal = {BMC neuroscience},
year = {2026},
month = jul,
doi = {10.1186/s12868-026-01029-y},
url = {https://europepmc.org/article/MED/42897467},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A single-cell atlas of intracranial aneurysm progression identifies a dysfunctional VSMC subpopulation associated with rupture risk.
AU - Xiangrong Chen
AU - Bikun Liu
AU - Xiaofeng Zhou
AU - Zongtao Wu
AU - Dongze Xu
AU - Jingcheng Zhan
AU - Jinliang Liu
AU - Mao Ling
AU - Fan Liu
PY - 2026
DA - 2026/07/01
JO - BMC neuroscience
DO - 10.1186/s12868-026-01029-y
UR - https://europepmc.org/article/MED/42897467
AB - Background Intracranial aneurysm (IA) rupture is a life-threatening event. While inflammation is implicated, the cellular mechanisms associated with progression from stable lesion to rupture remain poorly defined at single-cell resolution.Methods We performed single-cell RNA sequencing (scRNA-seq) on a mouse model spanning sham, formed, and ruptured IA stages. Computational analyses included trajectory inference, cell-cell communication analysis, and metabolic scoring. Key findings were validated using human IA bulk RNA-seq data and protein-level assays on matched clinical tissues.Results Our single-cell atlas revealed a progressive "inflammatory-lytic" microenvironment marked by immune cell infiltration and vascular smooth muscle cell (VSMC) depletion. We identified a metabolically specialized VSMC subpopulation (VSMC_0) that was selectively lost in formed and ruptured aneurysms. Pseudotime analysis indicated VSMC differentiation blockade, associated with downregulation of the structural genes actin alpha2, smooth muscle (ACTA2) and prolyl 4-hydroxylase subunit alpha2 (P4HA2), which correlated with irregular aneurysm shape a strong clinical predictor of rupture risk. Cell communication analysis positioned VSMC_0 as a signaling hub to macrophages, suggesting a feed-forward inflammatory loop. These findings were validated in human IAs tissues.Conclusion Our study identifies VSMC phenotypic dysregulation as a key correlate of IA instability, linking molecular deficits to clinical rupture predictors. This reframes IA as a disorder of vascular cellular identity and communication, revealing potential therapeutic targets for aneurysm stabilization.
SN - 1471-2202
ER -