Single-Cell RNA Sequencing Reveals the Pathogenic Relevance of Intracranial Atherosclerosis in Blood Blister-Like Aneurysms
BackgroundIntracranial non-branching site blood blister-like aneurysms (BBA) are extremely rare and vicious. Their etiology remains elusive, and no molecular study has been carried out to reveal its pathogenic relevance to intracranial atherosclerosis. To investigate its transcriptomic landscape and...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-07-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.927125/full |
| _version_ | 1818114802090770432 |
|---|---|
| author | Dingke Wen Xing Wang Ruiqi Chen Hao Li Jun Zheng Wei Fu Tianjie Zhang Mu Yang Chao You Lu Ma |
| author_facet | Dingke Wen Xing Wang Ruiqi Chen Hao Li Jun Zheng Wei Fu Tianjie Zhang Mu Yang Chao You Lu Ma |
| author_sort | Dingke Wen |
| collection | DOAJ |
| description | BackgroundIntracranial non-branching site blood blister-like aneurysms (BBA) are extremely rare and vicious. Their etiology remains elusive, and no molecular study has been carried out to reveal its pathogenic relevance to intracranial atherosclerosis. To investigate its transcriptomic landscape and underlying potential pathogenesis, we performed single-cell RNA sequencing with extensive pathological validation.MethodsIn total, 12,245 cells were recovered for single-cell RNA sequencing analysis from 1 BBA and 2 saccular intracranial aneurysms (IAs). Unbiased clustering using Seurat-based pipeline was used for cellular landscape profiling. Cellchat was used to understand intracellular communications. Furthermore, 10 BBAs and 30 IAs were retrospectively collected for pathological validations like scanning electron microscopy, H&E stain, Masson stain, Verhoeff Van Gielson stain, and immunofluorescence.ResultsSingle-cell transcriptome profiled 14 total subclusters in 6 major groups, namely, 6 monocyte/macrophage clusters, 2 T&NK clusters, 3 vascular smooth muscle cell (VSMC) clusters, 1 dendritic cell, 1 B cell, and 1 endothelial cell cluster. The only mural cell identified in BBAs was VSMC-2 cluster, while mural cells in IAs comprise most clusters of VSMCs and endothelial cells. Upregulated genes in BBA-derived VSMCs are related to arterial mineralization and atherosclerosis, such as PTX3, SPP1, LOX, etc., whereas vasodilation and physiological regulatory genes such as MGP, ACTA2, and MYL9 were conversely enriched in conventional IA-derived VSMCs. Immune cells in the BBA were predominantly macrophages, with a low fraction of T&NK cells, while conventional IAs had a higher percentage of T&NK. Gene enrichment analysis suggested that macrophages in BBA were highly enriched in lipid metabolism as well as atherosclerosis. Ligand–receptor interaction suggested that secretory phosphoprotein 1 (also known as osteopontin) played a major role in mediating the intracellular communication between VSMC and macrophages, especially in BBA. Pathological experiments corroborate with the bioinformatic findings and further characterized BBAs as a thin-walled thrombotic aneurysm with severe atherosclerotic lesions, where ApoE+ macrophages and OPN+ mural cells are intimately involved in the inflammation process.ConclusionsThe preexisting intracranial atherosclerosis might predispose the parent artery to the pathogenic occurrence of BBAs. These data shed light on the pathophysiology of intracranial aneurysms and might assist in the further resolution of the complexity in aneurysm pathogenesis. |
| first_indexed | 2024-12-11T03:56:31Z |
| format | Article |
| id | doaj.art-10a7f378df59409a8a0e5dc6acff7685 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T03:56:31Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-10a7f378df59409a8a0e5dc6acff76852022-12-22T01:21:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-07-011310.3389/fimmu.2022.927125927125Single-Cell RNA Sequencing Reveals the Pathogenic Relevance of Intracranial Atherosclerosis in Blood Blister-Like AneurysmsDingke Wen0Xing Wang1Ruiqi Chen2Hao Li3Jun Zheng4Wei Fu5Tianjie Zhang6Mu Yang7Chao You8Lu Ma9Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, Chengdu, ChinaRadiation Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital and Institute, University of Electronic and Science Technology of China, Chengdu, ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Neurosurgery, West China Hospital, Sichuan University, Chengdu, ChinaBackgroundIntracranial non-branching site blood blister-like aneurysms (BBA) are extremely rare and vicious. Their etiology remains elusive, and no molecular study has been carried out to reveal its pathogenic relevance to intracranial atherosclerosis. To investigate its transcriptomic landscape and underlying potential pathogenesis, we performed single-cell RNA sequencing with extensive pathological validation.MethodsIn total, 12,245 cells were recovered for single-cell RNA sequencing analysis from 1 BBA and 2 saccular intracranial aneurysms (IAs). Unbiased clustering using Seurat-based pipeline was used for cellular landscape profiling. Cellchat was used to understand intracellular communications. Furthermore, 10 BBAs and 30 IAs were retrospectively collected for pathological validations like scanning electron microscopy, H&E stain, Masson stain, Verhoeff Van Gielson stain, and immunofluorescence.ResultsSingle-cell transcriptome profiled 14 total subclusters in 6 major groups, namely, 6 monocyte/macrophage clusters, 2 T&NK clusters, 3 vascular smooth muscle cell (VSMC) clusters, 1 dendritic cell, 1 B cell, and 1 endothelial cell cluster. The only mural cell identified in BBAs was VSMC-2 cluster, while mural cells in IAs comprise most clusters of VSMCs and endothelial cells. Upregulated genes in BBA-derived VSMCs are related to arterial mineralization and atherosclerosis, such as PTX3, SPP1, LOX, etc., whereas vasodilation and physiological regulatory genes such as MGP, ACTA2, and MYL9 were conversely enriched in conventional IA-derived VSMCs. Immune cells in the BBA were predominantly macrophages, with a low fraction of T&NK cells, while conventional IAs had a higher percentage of T&NK. Gene enrichment analysis suggested that macrophages in BBA were highly enriched in lipid metabolism as well as atherosclerosis. Ligand–receptor interaction suggested that secretory phosphoprotein 1 (also known as osteopontin) played a major role in mediating the intracellular communication between VSMC and macrophages, especially in BBA. Pathological experiments corroborate with the bioinformatic findings and further characterized BBAs as a thin-walled thrombotic aneurysm with severe atherosclerotic lesions, where ApoE+ macrophages and OPN+ mural cells are intimately involved in the inflammation process.ConclusionsThe preexisting intracranial atherosclerosis might predispose the parent artery to the pathogenic occurrence of BBAs. These data shed light on the pathophysiology of intracranial aneurysms and might assist in the further resolution of the complexity in aneurysm pathogenesis.https://www.frontiersin.org/articles/10.3389/fimmu.2022.927125/fullblood blister-like aneurysmatherosclerosispathogenesispathologysingle-cell RNA sequencing |
| spellingShingle | Dingke Wen Xing Wang Ruiqi Chen Hao Li Jun Zheng Wei Fu Tianjie Zhang Mu Yang Chao You Lu Ma Single-Cell RNA Sequencing Reveals the Pathogenic Relevance of Intracranial Atherosclerosis in Blood Blister-Like Aneurysms Frontiers in Immunology blood blister-like aneurysm atherosclerosis pathogenesis pathology single-cell RNA sequencing |
| title | Single-Cell RNA Sequencing Reveals the Pathogenic Relevance of Intracranial Atherosclerosis in Blood Blister-Like Aneurysms |
| title_full | Single-Cell RNA Sequencing Reveals the Pathogenic Relevance of Intracranial Atherosclerosis in Blood Blister-Like Aneurysms |
| title_fullStr | Single-Cell RNA Sequencing Reveals the Pathogenic Relevance of Intracranial Atherosclerosis in Blood Blister-Like Aneurysms |
| title_full_unstemmed | Single-Cell RNA Sequencing Reveals the Pathogenic Relevance of Intracranial Atherosclerosis in Blood Blister-Like Aneurysms |
| title_short | Single-Cell RNA Sequencing Reveals the Pathogenic Relevance of Intracranial Atherosclerosis in Blood Blister-Like Aneurysms |
| title_sort | single cell rna sequencing reveals the pathogenic relevance of intracranial atherosclerosis in blood blister like aneurysms |
| topic | blood blister-like aneurysm atherosclerosis pathogenesis pathology single-cell RNA sequencing |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.927125/full |
| work_keys_str_mv | AT dingkewen singlecellrnasequencingrevealsthepathogenicrelevanceofintracranialatherosclerosisinbloodblisterlikeaneurysms AT xingwang singlecellrnasequencingrevealsthepathogenicrelevanceofintracranialatherosclerosisinbloodblisterlikeaneurysms AT ruiqichen singlecellrnasequencingrevealsthepathogenicrelevanceofintracranialatherosclerosisinbloodblisterlikeaneurysms AT haoli singlecellrnasequencingrevealsthepathogenicrelevanceofintracranialatherosclerosisinbloodblisterlikeaneurysms AT junzheng singlecellrnasequencingrevealsthepathogenicrelevanceofintracranialatherosclerosisinbloodblisterlikeaneurysms AT weifu singlecellrnasequencingrevealsthepathogenicrelevanceofintracranialatherosclerosisinbloodblisterlikeaneurysms AT tianjiezhang singlecellrnasequencingrevealsthepathogenicrelevanceofintracranialatherosclerosisinbloodblisterlikeaneurysms AT muyang singlecellrnasequencingrevealsthepathogenicrelevanceofintracranialatherosclerosisinbloodblisterlikeaneurysms AT chaoyou singlecellrnasequencingrevealsthepathogenicrelevanceofintracranialatherosclerosisinbloodblisterlikeaneurysms AT luma singlecellrnasequencingrevealsthepathogenicrelevanceofintracranialatherosclerosisinbloodblisterlikeaneurysms |