T cell-related diagnostic model and the underlying mechanism related to PRF1-mediated glycolysis in sepsis: evidences from single-cell, bulk transcriptomics, and experiment validation
Abstract Aim Sepsis is a serious systemic inflammatory response. We aimed to construct a T cell-related diagnostic model for sepsis and uncover the underlying mechanisms. Methods Through downloading the single-cell RNA-sequencing (scRNA-seq) and RNA-seq data from online source, a series of bioinform...
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BMC
2025-08-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02956-y |
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| author | Fu Tian Hui Chen Zhicheng Huang Kai Qiu |
| author_facet | Fu Tian Hui Chen Zhicheng Huang Kai Qiu |
| author_sort | Fu Tian |
| collection | DOAJ |
| description | Abstract Aim Sepsis is a serious systemic inflammatory response. We aimed to construct a T cell-related diagnostic model for sepsis and uncover the underlying mechanisms. Methods Through downloading the single-cell RNA-sequencing (scRNA-seq) and RNA-seq data from online source, a series of bioinformatics methods including principal component analysis (PCA), differential expression analysis, and least absolute shrinkage and selection operator (LASSO) was used for selection of the T cell-related signatures. Then a diagnostic model was constructed and receiver operator characteristic (ROC) curve was used for evaluation of the diagnostic ability. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for the function and pathways enrichment analysis. Metabolic flux analysis was performed to investigate the underlying metabolic mechanism. Finally, cecal ligation and puncture (CLP)-induced mouse sepsis model and LPS-induced RAW264.7 macrophage cell sepsis model were utilized to investigate the PRF1-mediated glycolysis mechanism in sepsis. Results scRNA-seq emphasized the important roles of T cell especially CD8+ T cell in sepsis. T cell-related differential genes were mainly enriched in T cell behavior and infection-related functions. A 15-gene diagnostic model related to T cell was constructed and validated to be effective in predicting the sepsis status. The most overexpressed gene PRF1 in T cell was related to glycolysis-related metabolic process including G3P → 3PD, 3PD → pyruvate, G3P → PRPP, and G6P → G3P. PRF1, inflammatory factors (TNF-α and IL-1β), lactate level, and glycolysis-related markers (PFKFB3, PKM2, and GLUT1) were increased and the ratio of CD4+/CD8+ T cells was decreased in vivo and in vitro sepsis models. But PRF1 knockdown significantly decreased the inflammatory factors (TNF-α and IL-1β), lactate levels, and glycolysis-related markers (PFKFB3, PKM2, and GLUT1) in sepsis. Conclusion A 15-gene T cell-related diagnostic model for sepsis is constructed and PRF1 is confirmed to be an effective indicator and therapeutic target for sepsis, mainly functions in glycolysis. |
| format | Article |
| id | doaj-art-a2a41132219c44aea9b1e0acd2a4a642 |
| institution | Kabale University |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-a2a41132219c44aea9b1e0acd2a4a6422025-08-20T04:01:56ZengBMCEuropean Journal of Medical Research2047-783X2025-08-0130111310.1186/s40001-025-02956-yT cell-related diagnostic model and the underlying mechanism related to PRF1-mediated glycolysis in sepsis: evidences from single-cell, bulk transcriptomics, and experiment validationFu Tian0Hui Chen1Zhicheng Huang2Kai Qiu3Department of Intensive Care Unit, Hangzhou Geriatric HospitalDepartment of Intensive Care Unit, Hangzhou Geriatric HospitalDepartment of Intensive Care Unit, Hangzhou Geriatric HospitalDepartment of Intensive Care Unit, Hangzhou Geriatric HospitalAbstract Aim Sepsis is a serious systemic inflammatory response. We aimed to construct a T cell-related diagnostic model for sepsis and uncover the underlying mechanisms. Methods Through downloading the single-cell RNA-sequencing (scRNA-seq) and RNA-seq data from online source, a series of bioinformatics methods including principal component analysis (PCA), differential expression analysis, and least absolute shrinkage and selection operator (LASSO) was used for selection of the T cell-related signatures. Then a diagnostic model was constructed and receiver operator characteristic (ROC) curve was used for evaluation of the diagnostic ability. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for the function and pathways enrichment analysis. Metabolic flux analysis was performed to investigate the underlying metabolic mechanism. Finally, cecal ligation and puncture (CLP)-induced mouse sepsis model and LPS-induced RAW264.7 macrophage cell sepsis model were utilized to investigate the PRF1-mediated glycolysis mechanism in sepsis. Results scRNA-seq emphasized the important roles of T cell especially CD8+ T cell in sepsis. T cell-related differential genes were mainly enriched in T cell behavior and infection-related functions. A 15-gene diagnostic model related to T cell was constructed and validated to be effective in predicting the sepsis status. The most overexpressed gene PRF1 in T cell was related to glycolysis-related metabolic process including G3P → 3PD, 3PD → pyruvate, G3P → PRPP, and G6P → G3P. PRF1, inflammatory factors (TNF-α and IL-1β), lactate level, and glycolysis-related markers (PFKFB3, PKM2, and GLUT1) were increased and the ratio of CD4+/CD8+ T cells was decreased in vivo and in vitro sepsis models. But PRF1 knockdown significantly decreased the inflammatory factors (TNF-α and IL-1β), lactate levels, and glycolysis-related markers (PFKFB3, PKM2, and GLUT1) in sepsis. Conclusion A 15-gene T cell-related diagnostic model for sepsis is constructed and PRF1 is confirmed to be an effective indicator and therapeutic target for sepsis, mainly functions in glycolysis.https://doi.org/10.1186/s40001-025-02956-ySepsisCD8+ T cellPRF1Glycolysis |
| spellingShingle | Fu Tian Hui Chen Zhicheng Huang Kai Qiu T cell-related diagnostic model and the underlying mechanism related to PRF1-mediated glycolysis in sepsis: evidences from single-cell, bulk transcriptomics, and experiment validation European Journal of Medical Research Sepsis CD8+ T cell PRF1 Glycolysis |
| title | T cell-related diagnostic model and the underlying mechanism related to PRF1-mediated glycolysis in sepsis: evidences from single-cell, bulk transcriptomics, and experiment validation |
| title_full | T cell-related diagnostic model and the underlying mechanism related to PRF1-mediated glycolysis in sepsis: evidences from single-cell, bulk transcriptomics, and experiment validation |
| title_fullStr | T cell-related diagnostic model and the underlying mechanism related to PRF1-mediated glycolysis in sepsis: evidences from single-cell, bulk transcriptomics, and experiment validation |
| title_full_unstemmed | T cell-related diagnostic model and the underlying mechanism related to PRF1-mediated glycolysis in sepsis: evidences from single-cell, bulk transcriptomics, and experiment validation |
| title_short | T cell-related diagnostic model and the underlying mechanism related to PRF1-mediated glycolysis in sepsis: evidences from single-cell, bulk transcriptomics, and experiment validation |
| title_sort | t cell related diagnostic model and the underlying mechanism related to prf1 mediated glycolysis in sepsis evidences from single cell bulk transcriptomics and experiment validation |
| topic | Sepsis CD8+ T cell PRF1 Glycolysis |
| url | https://doi.org/10.1186/s40001-025-02956-y |
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