{"title":"单核转录组分析揭示脑出血后神经炎症和髓鞘修复的时间动态。","authors":"Zhan Chen, Qinglin Wang, Rong Xiang, Ruoqi Ding, Jin Tao, Qinfeng Peng, Shaoshuai Wang, Nannan Cheng, Mengke Zhao, Jiaxin Li, Qidi Xue, Chuanyu Liu, Xuemei Chen, Longqi Liu, Junmin Wang, Jian Wang, Mingyue Wang","doi":"10.1002/ctm2.70486","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Intracerebral haemorrhage (ICH) progresses rapidly with complex pathology and limited treatment options, making it a severe subtype of stroke. The extravasation of blood into the brain parenchyma triggers a cascade of inflammatory responses, contributing to secondary injury. Single-nucleus RNA sequencing (snRNA-seq) data have enabled more profound insights into the cellular heterogeneity and dynamic interactions within the haemorrhagic brain. Immune cells play a crucial role in shaping neuroinflammation. However, the lack of comprehensive longitudinal studies limits our understanding of the temporal evolution of these inflammatory processes, posing a challenge to the development of targeted therapeutic strategies.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We used snRNA-seq in collagenase-induced ICH mouse models at Days 1, 3, 7, 14 and 28 post-injury, alongside naive controls, to profile the dynamics of gene expression over time.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>We obtained 281 577 high-quality transcriptional profiles representing 21 distinct cell types. Co-expression network analysis revealed a prominent ‘inflammation module’ that remained active throughout ICH. Integrative single-cell transcriptomic and immunofluorescence staining suggested that the various <i>Mif</i>-expressing cells may contribute to local inflammation, potentially engaging macrophages via receptor–ligand pairs such as <i>Cd44</i> and <i>Cd74</i>. Over time, microglia appeared to serve as key recipients of pro-inflammatory signals increasingly. During the resolution phase, oligodendrocytes exhibited transcriptional signatures consistent with enhanced maturation and remyelination, which T cell-mediated interactions may have facilitated.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>These findings offer a systems-level perspective on cell-type–specific responses and immune-mediated interactions during ICH progression and resolution.</p>\n </section>\n \n <section>\n \n <h3> Key points</h3>\n \n <div>\n <ul>\n \n <li>Establish intracerebral haemorrhage (ICH) mouse models at various time points (Days 1, 3, 7, 14, 28) and construct a high-quality single-nucleus RNA sequencing (snRNA-seq) atlas.</li>\n \n <li>Computational analyses suggest that macrophage recruitment in the early stage of ICH potentially involves migration inhibitory factor (MIF) signalling pathways.</li>\n \n <li>T cells may interact with myelin-forming oligodendrocytes during the resolution phase, potentially contributing to remyelination after ICH.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 10","pages":""},"PeriodicalIF":6.8000,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477064/pdf/","citationCount":"0","resultStr":"{\"title\":\"Single-nucleus transcriptomic profiling reveals temporal dynamics of neuroinflammation and myelin repair after intracerebral haemorrhage\",\"authors\":\"Zhan Chen, Qinglin Wang, Rong Xiang, Ruoqi Ding, Jin Tao, Qinfeng Peng, Shaoshuai Wang, Nannan Cheng, Mengke Zhao, Jiaxin Li, Qidi Xue, Chuanyu Liu, Xuemei Chen, Longqi Liu, Junmin Wang, Jian Wang, Mingyue Wang\",\"doi\":\"10.1002/ctm2.70486\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background</h3>\\n \\n <p>Intracerebral haemorrhage (ICH) progresses rapidly with complex pathology and limited treatment options, making it a severe subtype of stroke. The extravasation of blood into the brain parenchyma triggers a cascade of inflammatory responses, contributing to secondary injury. Single-nucleus RNA sequencing (snRNA-seq) data have enabled more profound insights into the cellular heterogeneity and dynamic interactions within the haemorrhagic brain. Immune cells play a crucial role in shaping neuroinflammation. However, the lack of comprehensive longitudinal studies limits our understanding of the temporal evolution of these inflammatory processes, posing a challenge to the development of targeted therapeutic strategies.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We used snRNA-seq in collagenase-induced ICH mouse models at Days 1, 3, 7, 14 and 28 post-injury, alongside naive controls, to profile the dynamics of gene expression over time.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>We obtained 281 577 high-quality transcriptional profiles representing 21 distinct cell types. Co-expression network analysis revealed a prominent ‘inflammation module’ that remained active throughout ICH. Integrative single-cell transcriptomic and immunofluorescence staining suggested that the various <i>Mif</i>-expressing cells may contribute to local inflammation, potentially engaging macrophages via receptor–ligand pairs such as <i>Cd44</i> and <i>Cd74</i>. Over time, microglia appeared to serve as key recipients of pro-inflammatory signals increasingly. During the resolution phase, oligodendrocytes exhibited transcriptional signatures consistent with enhanced maturation and remyelination, which T cell-mediated interactions may have facilitated.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>These findings offer a systems-level perspective on cell-type–specific responses and immune-mediated interactions during ICH progression and resolution.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Key points</h3>\\n \\n <div>\\n <ul>\\n \\n <li>Establish intracerebral haemorrhage (ICH) mouse models at various time points (Days 1, 3, 7, 14, 28) and construct a high-quality single-nucleus RNA sequencing (snRNA-seq) atlas.</li>\\n \\n <li>Computational analyses suggest that macrophage recruitment in the early stage of ICH potentially involves migration inhibitory factor (MIF) signalling pathways.</li>\\n \\n <li>T cells may interact with myelin-forming oligodendrocytes during the resolution phase, potentially contributing to remyelination after ICH.</li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":10189,\"journal\":{\"name\":\"Clinical and Translational Medicine\",\"volume\":\"15 10\",\"pages\":\"\"},\"PeriodicalIF\":6.8000,\"publicationDate\":\"2025-09-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477064/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Translational Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70486\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70486","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Single-nucleus transcriptomic profiling reveals temporal dynamics of neuroinflammation and myelin repair after intracerebral haemorrhage
Background
Intracerebral haemorrhage (ICH) progresses rapidly with complex pathology and limited treatment options, making it a severe subtype of stroke. The extravasation of blood into the brain parenchyma triggers a cascade of inflammatory responses, contributing to secondary injury. Single-nucleus RNA sequencing (snRNA-seq) data have enabled more profound insights into the cellular heterogeneity and dynamic interactions within the haemorrhagic brain. Immune cells play a crucial role in shaping neuroinflammation. However, the lack of comprehensive longitudinal studies limits our understanding of the temporal evolution of these inflammatory processes, posing a challenge to the development of targeted therapeutic strategies.
Methods
We used snRNA-seq in collagenase-induced ICH mouse models at Days 1, 3, 7, 14 and 28 post-injury, alongside naive controls, to profile the dynamics of gene expression over time.
Results
We obtained 281 577 high-quality transcriptional profiles representing 21 distinct cell types. Co-expression network analysis revealed a prominent ‘inflammation module’ that remained active throughout ICH. Integrative single-cell transcriptomic and immunofluorescence staining suggested that the various Mif-expressing cells may contribute to local inflammation, potentially engaging macrophages via receptor–ligand pairs such as Cd44 and Cd74. Over time, microglia appeared to serve as key recipients of pro-inflammatory signals increasingly. During the resolution phase, oligodendrocytes exhibited transcriptional signatures consistent with enhanced maturation and remyelination, which T cell-mediated interactions may have facilitated.
Conclusions
These findings offer a systems-level perspective on cell-type–specific responses and immune-mediated interactions during ICH progression and resolution.
Key points
Establish intracerebral haemorrhage (ICH) mouse models at various time points (Days 1, 3, 7, 14, 28) and construct a high-quality single-nucleus RNA sequencing (snRNA-seq) atlas.
Computational analyses suggest that macrophage recruitment in the early stage of ICH potentially involves migration inhibitory factor (MIF) signalling pathways.
T cells may interact with myelin-forming oligodendrocytes during the resolution phase, potentially contributing to remyelination after ICH.
期刊介绍：
Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.
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