Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered ...Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.展开更多
Background:Glioblastoma is one of the most common primary intracranial tumors of the central nervous system in adults.Although chemotherapy is an important component of glioblastoma treatment,its effectiveness remains...Background:Glioblastoma is one of the most common primary intracranial tumors of the central nervous system in adults.Although chemotherapy is an important component of glioblastoma treatment,its effectiveness remains unsatisfactory.Due to multiple immunosuppressive mechanisms,glioblastoma immunotherapy has not been effective in treating many patients as a result of the clinical breakthroughs in the field.Therefore,the development of cancer immunotherapy relies on the understanding of how tumors interact with the immune system and the analysis of their molecular determinants.This study identified the key interactions between immune cells in the glioma microenvironment using RNA microarrays and single-cell sequencing.Methods:First,we screened differentially expressed genes in tumor and control samples from GSE29796 and GSE50161 datasets using GEO2R.All differentially expressed genes were used to perform enrichment analysis and construct protein-protein interaction topological analysis to analyze the interaction between proteins.Using single-cell RNA sequencing data from the GSE162631 database,we identified immune cell types within the glioblastoma microenvironment,and validated the hub gene expression in these cells.In addition,based on the GEPIA and TIMER databases,hub genes were investigated and compared with immune infiltration to determine differential expression.Finally,CellChat was used to visualize the gene expression distribution and cell-to-cell communication analysis of the proteins between different types of cells.Results:We found that monocytes/macrophages may communicate with each other in the tumor microenvironment through MIF-(CD74+CXCR4)and MIF-(CD74+CD44).In addition,our study indicated that celastrol has the ability to inhibit inflammatory factors expression by MIF/CD74 signaling pathway in U87 cells.Conclusion:This study improved the effectiveness of cancer immunotherapy strategies and developed new ideas for immunotherapy that can be applied to glioblastoma.展开更多
基金partially supported by the Natural Science Foundation of Zhejiang Province(Award number:D21C170001)the National Natural Science Foundation of China(Award number:31973000)。
文摘Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.
基金supported by the National Natural Science Foundation of China(No.82204663)the Natural Science Foundation of Shandong Province(No.ZR2022QH058).
文摘Background:Glioblastoma is one of the most common primary intracranial tumors of the central nervous system in adults.Although chemotherapy is an important component of glioblastoma treatment,its effectiveness remains unsatisfactory.Due to multiple immunosuppressive mechanisms,glioblastoma immunotherapy has not been effective in treating many patients as a result of the clinical breakthroughs in the field.Therefore,the development of cancer immunotherapy relies on the understanding of how tumors interact with the immune system and the analysis of their molecular determinants.This study identified the key interactions between immune cells in the glioma microenvironment using RNA microarrays and single-cell sequencing.Methods:First,we screened differentially expressed genes in tumor and control samples from GSE29796 and GSE50161 datasets using GEO2R.All differentially expressed genes were used to perform enrichment analysis and construct protein-protein interaction topological analysis to analyze the interaction between proteins.Using single-cell RNA sequencing data from the GSE162631 database,we identified immune cell types within the glioblastoma microenvironment,and validated the hub gene expression in these cells.In addition,based on the GEPIA and TIMER databases,hub genes were investigated and compared with immune infiltration to determine differential expression.Finally,CellChat was used to visualize the gene expression distribution and cell-to-cell communication analysis of the proteins between different types of cells.Results:We found that monocytes/macrophages may communicate with each other in the tumor microenvironment through MIF-(CD74+CXCR4)and MIF-(CD74+CD44).In addition,our study indicated that celastrol has the ability to inhibit inflammatory factors expression by MIF/CD74 signaling pathway in U87 cells.Conclusion:This study improved the effectiveness of cancer immunotherapy strategies and developed new ideas for immunotherapy that can be applied to glioblastoma.
