Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single-Cell RNA Sequencing

Hang Ji ¹, Yue Li ¹, Haogeng Sun ¹

⁰Department of Neurosurgery, West China Hospital Sichuan University Chengdu China.

Journal of the American Heart Association +

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February 23, 2024

View abstract on PubMed

Summary

This study reveals distinct cell populations in intracranial aneurysms (IA), identifying macrophages as key players in IA rupture. These findings may guide new treatments for unruptured IA.

Area Of Science

Vascular Biology
Immunology
Genomics

Background

Intracranial aneurysms (IA) are common and can cause fatal hemorrhagic strokes.
The cellular composition and inflammatory processes within IA domes are not well understood.

Purpose Of The Study

To delineate the cell atlas and inflammatory features of human IA domes using single-cell RNA sequencing.
To identify cellular differences between ruptured and unruptured IAs and their association with rupture.

Main Methods

Single-cell RNA sequencing of human IA domes.
Validation using external bulk mRNA sequencing data and patient serology.
Immunofluorescence staining and machine learning algorithms.

Main Results

21,332 cells were analyzed, revealing sparse vascular cells (4.84%) and abundant immune cells.
Pericytes were identified in the IA dome for the first time.
Macrophages and neutrophils were significantly increased in ruptured IAs; macrophages were robustly associated with rupture.
A specific SNP (rs2280543) linked to macrophage metabolic reprogramming via TALDO1.

Conclusions

Provides a detailed cellular map of the IA dome.
Highlights the role of macrophages in IA rupture.
Suggests potential therapeutic targets for unruptured IA.

Keywords:

human intracranial aneurysm inflammation macrophage pericyte single‐cell transcriptome