Single‐Cell Transcriptomes of Immune Cells from Multiple Compartments Redefine the Ontology of Myeloid Subtypes Post‐Stroke
Abstract The activation and infiltration of immune cells are hallmarks of ischemic stroke. However, the precise origins and the molecular alterations of these infiltrating cells post‐stroke remain poorly characterized. Here, a murine model of stroke (permanent middle cerebral artery occlusion [p‐MCA...
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Wiley
2025-04-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408722 |
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| author | Mo Yang Yixiang Li Kaibin Shi Xuezhu Wang Xiangrong Liu Xiang Huang Fu‐Dong Shi Shaojie Ma Mingfeng Li Yilong Wang |
| author_facet | Mo Yang Yixiang Li Kaibin Shi Xuezhu Wang Xiangrong Liu Xiang Huang Fu‐Dong Shi Shaojie Ma Mingfeng Li Yilong Wang |
| author_sort | Mo Yang |
| collection | DOAJ |
| description | Abstract The activation and infiltration of immune cells are hallmarks of ischemic stroke. However, the precise origins and the molecular alterations of these infiltrating cells post‐stroke remain poorly characterized. Here, a murine model of stroke (permanent middle cerebral artery occlusion [p‐MCAO]) is utilized to profile single‐cell transcriptomes of immune cells in the brain and their potential origins, including the calvarial bone marrow (CBM), femur bone marrow (FBM), and peripheral blood mononuclear cells (PBMCs). This analysis reveals transcriptomically distinct populations of cerebral myeloid cells and brain‐resident immune cells after stroke. These include a novel CD14+ neutrophil subpopulation that transcriptomically resembles CBM neutrophils. Moreover, the sequential activation of transcription factor regulatory networks in neutrophils during stroke progression is delineated, many of which are unique to the CD14+ population and underlie their acquisition of chemotaxis and granule release capacities. Two distinct origins of post‐stroke disease‐related immune cell subtypes are also identified: disease inflammatory macrophages, likely deriving from circulating monocytes in the skull, and transcriptionally immature disease‐associated microglia, possibly arising from pre‐existing homeostatic microglia. Together, a comprehensive molecular survey of post‐stroke immune responses is performed, encompassing both local and distant bone marrow sites and peripheral blood. |
| format | Article |
| id | doaj-art-b51184d3e6404dc6a328879787787046 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-b51184d3e6404dc6a3288797877870462025-08-20T03:04:17ZengWileyAdvanced Science2198-38442025-04-011213n/an/a10.1002/advs.202408722Single‐Cell Transcriptomes of Immune Cells from Multiple Compartments Redefine the Ontology of Myeloid Subtypes Post‐StrokeMo Yang0Yixiang Li1Kaibin Shi2Xuezhu Wang3Xiangrong Liu4Xiang Huang5Fu‐Dong Shi6Shaojie Ma7Mingfeng Li8Yilong Wang9Department of Neurology Beijing Tiantan Hospital Capital Medical University Beijing 100070 ChinaDepartment of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaDepartment of Neurology Beijing Tiantan Hospital Capital Medical University Beijing 100070 ChinaDepartment of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaChina National Clinical Research Center for Neurological Diseases Beijing 100070 ChinaInstitute of Neuroscience CAS Center for Excellence in Brain Science and Intelligence Technology University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaDepartment of Neurology Beijing Tiantan Hospital Capital Medical University Beijing 100070 ChinaInstitute of Neuroscience CAS Center for Excellence in Brain Science and Intelligence Technology University of Chinese Academy of Sciences Chinese Academy of Sciences Shanghai 200031 ChinaDepartment of Pharmacology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaDepartment of Neurology Beijing Tiantan Hospital Capital Medical University Beijing 100070 ChinaAbstract The activation and infiltration of immune cells are hallmarks of ischemic stroke. However, the precise origins and the molecular alterations of these infiltrating cells post‐stroke remain poorly characterized. Here, a murine model of stroke (permanent middle cerebral artery occlusion [p‐MCAO]) is utilized to profile single‐cell transcriptomes of immune cells in the brain and their potential origins, including the calvarial bone marrow (CBM), femur bone marrow (FBM), and peripheral blood mononuclear cells (PBMCs). This analysis reveals transcriptomically distinct populations of cerebral myeloid cells and brain‐resident immune cells after stroke. These include a novel CD14+ neutrophil subpopulation that transcriptomically resembles CBM neutrophils. Moreover, the sequential activation of transcription factor regulatory networks in neutrophils during stroke progression is delineated, many of which are unique to the CD14+ population and underlie their acquisition of chemotaxis and granule release capacities. Two distinct origins of post‐stroke disease‐related immune cell subtypes are also identified: disease inflammatory macrophages, likely deriving from circulating monocytes in the skull, and transcriptionally immature disease‐associated microglia, possibly arising from pre‐existing homeostatic microglia. Together, a comprehensive molecular survey of post‐stroke immune responses is performed, encompassing both local and distant bone marrow sites and peripheral blood.https://doi.org/10.1002/advs.202408722brainimmune cellsscRNA‐seqskull bone marrowstroke |
| spellingShingle | Mo Yang Yixiang Li Kaibin Shi Xuezhu Wang Xiangrong Liu Xiang Huang Fu‐Dong Shi Shaojie Ma Mingfeng Li Yilong Wang Single‐Cell Transcriptomes of Immune Cells from Multiple Compartments Redefine the Ontology of Myeloid Subtypes Post‐Stroke Advanced Science brain immune cells scRNA‐seq skull bone marrow stroke |
| title | Single‐Cell Transcriptomes of Immune Cells from Multiple Compartments Redefine the Ontology of Myeloid Subtypes Post‐Stroke |
| title_full | Single‐Cell Transcriptomes of Immune Cells from Multiple Compartments Redefine the Ontology of Myeloid Subtypes Post‐Stroke |
| title_fullStr | Single‐Cell Transcriptomes of Immune Cells from Multiple Compartments Redefine the Ontology of Myeloid Subtypes Post‐Stroke |
| title_full_unstemmed | Single‐Cell Transcriptomes of Immune Cells from Multiple Compartments Redefine the Ontology of Myeloid Subtypes Post‐Stroke |
| title_short | Single‐Cell Transcriptomes of Immune Cells from Multiple Compartments Redefine the Ontology of Myeloid Subtypes Post‐Stroke |
| title_sort | single cell transcriptomes of immune cells from multiple compartments redefine the ontology of myeloid subtypes post stroke |
| topic | brain immune cells scRNA‐seq skull bone marrow stroke |
| url | https://doi.org/10.1002/advs.202408722 |
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