Dataset Information

Systematic Study of the Immune Components after Ischemic Stroke Using CyTOF Techniques.

ABSTRACT: Stroke induces a robust inflammatory response. However, it still lacks a systematic view of the various immune cell types due to the limited numbers of fluorophore used in the traditional FACS technique. In our current study, we utilized the novel technique mass cytometry (CyTOF) to analyze multiple immune cell types. We detected these immune cells from the ischemic brain, peripheral blood, spleen, and bone marrow at different time courses after stroke. Our data showed (1) dynamic changes in the immune cell numbers in the ischemic brain and peripheral organs. (2) The expression levels of cell surface markers indicate the inflammation response status after stroke. Interestingly, CD62L, a key adhesion molecule, regulates the migration of leukocytes from blood vessels into secondary lymphoid tissues and peripheral tissues. (3) A strong leukocyte network across the brain and peripheral immune organs was identified using the R program at day 1 after ischemia, suggesting that the peripheral immune cells dramatically migrated into the ischemic areas after stroke. This study provides a systematic, wide view of the immune components in the brain and peripheral organs for a deep understanding of the immune response after ischemic stroke.

SUBMITTER: Li Y

PROVIDER: S-EPMC7474762 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Systematic Study of the Immune Components after Ischemic Stroke Using CyTOF Techniques.

Li Yaning Y Wang Yan Y Yao Yang Y Griffiths Brian B BB Feng Liangshu L Tao Tao T Wang Feng F Xu Baohui B Stary Creed M CM Zhao Heng H

Journal of immunology research 20200828

Stroke induces a robust inflammatory response. However, it still lacks a systematic view of the various immune cell types due to the limited numbers of fluorophore used in the traditional FACS technique. In our current study, we utilized the novel technique mass cytometry (CyTOF) to analyze multiple immune cell types. We detected these immune cells from the ischemic brain, peripheral blood, spleen, and bone marrow at different time courses after stroke. Our data showed (1) dynamic changes in the ...[more]

PMID: 32908941

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Project description:Background: Previous study showed that stroke may be a potential first sign of neoplasia. But the relationship between them remains unclear. Besides, ischemic stroke is a complex brain disease, which involves cell death or complex immune regulation. Thus, it is necessary to reveal the association of tumor immune microenvironment and cell death with ischemic stroke. Methods: Here, a photothrombosis-induced ischemic injury models of brain and skull was established. We compared and analyzed the pattern of gene expression profile between brain and skull after ischemic injury by transcriptome analysis. Further, we investigated the enrichment of relevant differential genes in cancer pathways and cell death pathways, and analyzed changes in the immune microenvironment after ischemic injury. Moreover, the pan-cancer genomic and prognosis analysis of ischemic injury related gene set were performed. Results: The results showed that the gene expression patterns were different in temporal and spatial locations after ischemic injury. We found that the effect on the transcriptome of the brain after skull ischemic injury was particularly large, but it could be recovered in a short period, while the effect on the skull after brain ischemic injury was long-lasting. The expression of genes related to ischemic injury is also associated with cell death and cancer hallmark pathways. In addition, changes in the abundance of immune cells indicate that brain ischemic injury may disrupt its immune microenvironment for a longer time, while skull can better balance the stability of immune microenvironment. Moreover, the brain ischemic injury-related gene sets are highly correlated with a variety of tumors, especially GBM, KIRC, LGG and UVM after stroke have a greater risk of death. Conclusion: This study gives us a new understanding of the role of the skull in brain ischemic injury, and reveals the association of tumor immune microenvironment and cell death with ischemic stroke.

Project description:The third leading cause of death in the United States, stroke is an acute neurological event leading to death of neural tissues. Although the majority of strokes are ischemic strokes, meaning there is oxygen deprivation to the brain, almost 20% of strokes are hemorrhagic, resulting from bleeding into the brain. Stroke is a complex disorder and likely multigenic in nature, resulting from a combination of genetic and environmental factors. These well characterized risk factors that contribute to the incidence of stroke include hypertension, cardiac disease, sickle cell disease, hyperhomocysteinemia, family history of stroke and smoking. ISGS aim is to perform a prospective genetic association study of ischemic stroke focusing on the hemostatic system. ISGS is a 5-center case-control study of first-ever ischemic stroke cases and concurrent controls individually matched for age, sex and recruitment site. This data includes that from subjects both banked in the <a href="http://ccr.coriell.org/Sections/Collections/NINDS/?SsId=10"> NINDS repository</a> with biologicals publicly available, and those whose samples are not banked/not available.  This study utilized the <a href="./study.cgi?id=phs000005">NINDS Repository Cerebrovascular/Stroke Study</a>, and <a href="./study.cgi?id=phs000004">neurologically normal controls</a> from the sample population which are banked in the National Institute of Neurological Disorders and Stroke (NINDS Repository) collection for a first stage whole genome analysis.

Project description:Ischemic stroke (IS) is a leading cause of death and disability worldwide. Screening for marker genes in IS is crucial for its early diagnosis and improvement in clinical outcomes. In the study, the gene expression profiles in the GSE22255 and GSE37587 datasets were extracted from the public database Gene Expression Omnibus. Weighted gene co‑expression network analysis (WGCNA) was used to investigate the gene sets that were related to ubiquitination. A total of 33 ubiquitination-related differentially expressed genes (DEGs) were identified using "limma (version 3.50.0)". Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) analysis enriched multiple pathways that were closely related to IS. The correlations between the HALLMARK signaling pathways and DGEs were analyzed. Receiver operating characteristic analysis was used to validate the diagnostic value of the key genes. Among them, 16 genes were identified as hub genes. Single-sample GSEA was performed to evaluate the infiltration status of immune cells in IS. To understand the potential molecular mechanisms of the hub genes in IS, we constructed RBP-mRNA and mRNA-miRNA-lncRNA interaction networks. Additionally, we used the GeneMANIA database to create a PPI network for the signature genes to investigate their functions. As a result, there was a significant difference in the overall infiltration of immune cells between the IS and control groups. Among the 28 types of immune cells, the degree of infiltration of seven types was significantly different between the two groups (p<0.05). The expression of four types of immune cells, namely type 1 T helper cell, type 17 T helper cell, eosinophil, and mast cell, in the IS group were significantly higher than that in the control group. The expressions of DHFR2 (R = -0.575; p<0.001) and DNAAF2 (R = -0.562; p<0.001) were significantly negatively correlated with eosinophil infiltration. The PPI network demonstrated that the 16 hub genes interacted with each other. In conclusion, we identified DEGs, WGCNA modules, hub genes, enriched pathways, and infiltrating immune cells that may be closely involved in IS. Further studies are required to explore the functions of these genes.

Dataset Information

Systematic Study of the Immune Components after Ischemic Stroke Using CyTOF Techniques.

Publications

Systematic Study of the Immune Components after Ischemic Stroke Using CyTOF Techniques.

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