Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single‐Cell RNA Sequencing
Background Intracranial aneurysm (IA) is common and occasionally results in life‐threatening hemorrhagic strokes. However, the cell architecture and inflammation in the IA dome remain less understood. Methods and Results Single‐cell RNA sequencing was performed on ruptured and unruptured human IA do...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-03-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.123.032456 |
| _version_ | 1797269148674293760 |
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| author | Hang Ji Yue Li Haogeng Sun Ruiqi Chen Ran Zhou Yongbo Yang Rong Wang Chao You Anqi Xiao Liu Yi |
| author_facet | Hang Ji Yue Li Haogeng Sun Ruiqi Chen Ran Zhou Yongbo Yang Rong Wang Chao You Anqi Xiao Liu Yi |
| author_sort | Hang Ji |
| collection | DOAJ |
| description | Background Intracranial aneurysm (IA) is common and occasionally results in life‐threatening hemorrhagic strokes. However, the cell architecture and inflammation in the IA dome remain less understood. Methods and Results Single‐cell RNA sequencing was performed on ruptured and unruptured human IA domes for delineating the cell atlas, gene expression perturbations, and inflammation features. Two external bulk mRNA sequencing–based data sets and serological results of 126 patients were collected for validation. As a result, a total of 21 332 qualified cells were captured. Vascular cells, including endothelial cells, smooth muscle cells, fibroblasts, and pericytes, were assigned in extremely sparse numbers (4.84%), and were confirmed by immunofluorescence staining. Pericytes, characterized by ABCC9 and HIGD1B, were identified in the IA dome for the first time. Abundant immune cells were identified, with the proportion of monocytes/macrophages and neutrophils being remarkably higher in ruptured IA. The lymphocyte compartment was also thoroughly categorized. By leveraging external data sets and machine learning algorithms, macrophages were robustly associated with IA rupture, irrespective of their polarization status. The single nucleotide polymorphism rs2280543, which is identified in East Asian populations, was associated with macrophage metabolic reprogramming through regulating TALDO1 expression. Conclusions This study provides insights into the cellular architecture and inflammatory features in the IA dome and may enlighten novel therapeutics for unruptured IA. |
| first_indexed | 2024-04-25T01:43:46Z |
| format | Article |
| id | doaj.art-f56708c911f841d08c6edf6e14313408 |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-25T01:43:46Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-f56708c911f841d08c6edf6e143134082024-03-08T02:22:47ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-03-0113510.1161/JAHA.123.032456Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single‐Cell RNA SequencingHang Ji0Yue Li1Haogeng Sun2Ruiqi Chen3Ran Zhou4Yongbo Yang5Rong Wang6Chao You7Anqi Xiao8Liu Yi9Department 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, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital Sichuan University Chengdu ChinaDepartment of Neurosurgery, Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Nanjing ChinaDepartment of Neurosurgery, Beijing Tiantan Hospital Capital Medical University Beijing 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 ChinaBackground Intracranial aneurysm (IA) is common and occasionally results in life‐threatening hemorrhagic strokes. However, the cell architecture and inflammation in the IA dome remain less understood. Methods and Results Single‐cell RNA sequencing was performed on ruptured and unruptured human IA domes for delineating the cell atlas, gene expression perturbations, and inflammation features. Two external bulk mRNA sequencing–based data sets and serological results of 126 patients were collected for validation. As a result, a total of 21 332 qualified cells were captured. Vascular cells, including endothelial cells, smooth muscle cells, fibroblasts, and pericytes, were assigned in extremely sparse numbers (4.84%), and were confirmed by immunofluorescence staining. Pericytes, characterized by ABCC9 and HIGD1B, were identified in the IA dome for the first time. Abundant immune cells were identified, with the proportion of monocytes/macrophages and neutrophils being remarkably higher in ruptured IA. The lymphocyte compartment was also thoroughly categorized. By leveraging external data sets and machine learning algorithms, macrophages were robustly associated with IA rupture, irrespective of their polarization status. The single nucleotide polymorphism rs2280543, which is identified in East Asian populations, was associated with macrophage metabolic reprogramming through regulating TALDO1 expression. Conclusions This study provides insights into the cellular architecture and inflammatory features in the IA dome and may enlighten novel therapeutics for unruptured IA.https://www.ahajournals.org/doi/10.1161/JAHA.123.032456human intracranial aneurysminflammationmacrophagepericytesingle‐cell transcriptome |
| spellingShingle | Hang Ji Yue Li Haogeng Sun Ruiqi Chen Ran Zhou Yongbo Yang Rong Wang Chao You Anqi Xiao Liu Yi Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single‐Cell RNA Sequencing Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease human intracranial aneurysm inflammation macrophage pericyte single‐cell transcriptome |
| title | Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single‐Cell RNA Sequencing |
| title_full | Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single‐Cell RNA Sequencing |
| title_fullStr | Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single‐Cell RNA Sequencing |
| title_full_unstemmed | Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single‐Cell RNA Sequencing |
| title_short | Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single‐Cell RNA Sequencing |
| title_sort | decoding the cell atlas and inflammatory features of human intracranial aneurysm wall by single cell rna sequencing |
| topic | human intracranial aneurysm inflammation macrophage pericyte single‐cell transcriptome |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.032456 |
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