Discrepancies between human and murine model cerebral aneurysms at single-cell resolution

BackgroundThe murine model of cerebral aneurysm (CA) serves as a prevalent tool for investigating the molecular underpinnings of CA. However, the extent to which the CA murine model aligns with that of human remains elusive.MethodsThe present study employed a comprehensive integration and exploratio...

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Main Authors: Hang Ji, Guicheng Kuang, Hailan Yang, Haitao Liu, Yue Li, Shaoshan Hu, Anqi Xiao, Chao You, Haogeng Sun, Chaofeng Fan, Guozhang Sun
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Cell and Developmental Biology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2025.1512938/full
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author Hang Ji
Hang Ji
Guicheng Kuang
Hailan Yang
Haitao Liu
Yue Li
Shaoshan Hu
Anqi Xiao
Chao You
Haogeng Sun
Chaofeng Fan
Guozhang Sun
author_facet Hang Ji
Hang Ji
Guicheng Kuang
Hailan Yang
Haitao Liu
Yue Li
Shaoshan Hu
Anqi Xiao
Chao You
Haogeng Sun
Chaofeng Fan
Guozhang Sun
author_sort Hang Ji
collection DOAJ
description BackgroundThe murine model of cerebral aneurysm (CA) serves as a prevalent tool for investigating the molecular underpinnings of CA. However, the extent to which the CA murine model aligns with that of human remains elusive.MethodsThe present study employed a comprehensive integration and exploration of the single-cell RNA-seq (scRNA-seq) datasets, along with multiple trajectory and gene regulatory network analyses, to investigate the cellular and molecular discrepancies between human and murine model CAs.ResultsThe uniform manifold approximation and projection (umap) embedding exhibits that the primary discrepancies between human and murine model CAs reside in the cells of modifiable phenotype, encompassing vascular smooth muscle cell (vSMC), monocyte/macrophage, and neutrophil. The vSMCs from human CA tissue exhibit a fibroblast-like phenotype in comparison to that of murine model. Distinct patterns of neutrophil recruitment are observed in human and murine models, with the former characterized by neutrophil-derived CXCL8 and the latter by monocyte/macrophage-derived CCLs. In addition, macrophages originated from human unruptured CA express higher levels of M2 gene markers. Moreover, the inflammatory status of the CA tissue differs between humans and mouse models, with the former exhibiting a more acute and intense inflammation.ConclusionThese findings demonstrate subtle but important disparities between human and murine model CAs, and may shed light upon an optimization of murine CA model.
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spelling doaj-art-e3066c72ca874637868e0af855e762922025-08-20T02:47:46ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-03-011310.3389/fcell.2025.15129381512938Discrepancies between human and murine model cerebral aneurysms at single-cell resolutionHang Ji0Hang Ji1Guicheng Kuang2Hailan Yang3Haitao Liu4Yue Li5Shaoshan Hu6Anqi Xiao7Chao You8Haogeng Sun9Chaofeng Fan10Guozhang Sun11Department of Neurosurgery, Sichuan University West China Hospital, Chengdu, ChinaDepartment of Neurosurgery, Zhejiang Provincial People’s Hospital, Hangzhou, ChinaDepartment of Neurosurgery, Sichuan University West China Hospital, Chengdu, ChinaDepartment of Neurosurgery, Sichuan University West China Hospital, Chengdu, ChinaDepartment of Neurosurgery, Sichuan University West China Hospital, Chengdu, ChinaDepartment of Neurosurgery, Sichuan University West China Hospital, Chengdu, ChinaDepartment of Neurosurgery, Zhejiang Provincial People’s Hospital, Hangzhou, ChinaDepartment of Neurosurgery, Sichuan University West China Hospital, Chengdu, ChinaDepartment of Neurosurgery, Sichuan University West China Hospital, Chengdu, ChinaDepartment of Neurosurgery, Sichuan University West China Hospital, Chengdu, ChinaDepartment of Neurosurgery, Sichuan University West China Hospital, Chengdu, ChinaDepartment of Neurosurgery, Hei Longjiang Provincial People’s Hospital, Harbin, Hei Longjiang, ChinaBackgroundThe murine model of cerebral aneurysm (CA) serves as a prevalent tool for investigating the molecular underpinnings of CA. However, the extent to which the CA murine model aligns with that of human remains elusive.MethodsThe present study employed a comprehensive integration and exploration of the single-cell RNA-seq (scRNA-seq) datasets, along with multiple trajectory and gene regulatory network analyses, to investigate the cellular and molecular discrepancies between human and murine model CAs.ResultsThe uniform manifold approximation and projection (umap) embedding exhibits that the primary discrepancies between human and murine model CAs reside in the cells of modifiable phenotype, encompassing vascular smooth muscle cell (vSMC), monocyte/macrophage, and neutrophil. The vSMCs from human CA tissue exhibit a fibroblast-like phenotype in comparison to that of murine model. Distinct patterns of neutrophil recruitment are observed in human and murine models, with the former characterized by neutrophil-derived CXCL8 and the latter by monocyte/macrophage-derived CCLs. In addition, macrophages originated from human unruptured CA express higher levels of M2 gene markers. Moreover, the inflammatory status of the CA tissue differs between humans and mouse models, with the former exhibiting a more acute and intense inflammation.ConclusionThese findings demonstrate subtle but important disparities between human and murine model CAs, and may shed light upon an optimization of murine CA model.https://www.frontiersin.org/articles/10.3389/fcell.2025.1512938/fullcerebral aneurysmhuman CAmurine model CAsingle-cell RNA sequencinginflammation
spellingShingle Hang Ji
Hang Ji
Guicheng Kuang
Hailan Yang
Haitao Liu
Yue Li
Shaoshan Hu
Anqi Xiao
Chao You
Haogeng Sun
Chaofeng Fan
Guozhang Sun
Discrepancies between human and murine model cerebral aneurysms at single-cell resolution
Frontiers in Cell and Developmental Biology
cerebral aneurysm
human CA
murine model CA
single-cell RNA sequencing
inflammation
title Discrepancies between human and murine model cerebral aneurysms at single-cell resolution
title_full Discrepancies between human and murine model cerebral aneurysms at single-cell resolution
title_fullStr Discrepancies between human and murine model cerebral aneurysms at single-cell resolution
title_full_unstemmed Discrepancies between human and murine model cerebral aneurysms at single-cell resolution
title_short Discrepancies between human and murine model cerebral aneurysms at single-cell resolution
title_sort discrepancies between human and murine model cerebral aneurysms at single cell resolution
topic cerebral aneurysm
human CA
murine model CA
single-cell RNA sequencing
inflammation
url https://www.frontiersin.org/articles/10.3389/fcell.2025.1512938/full
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