Project description:We report the use of single cell RNA sequencing to identify differentially-expressed genes in liver macrophages from a mouse model of Noonan syndrome (NS) and highlight specific subpopulation clusters that may contribute to the associated insulin resistance phenotype.
Project description:Liver fibrosis is a common pathological process in chronic liver disease, reflecting the advanced stage of the disease. Liver endothelial cells (ECs), especially liver sinusoidal endothelial cells (LSECs), are recognized as critical modulators of liver homeostasis and play essential roles in the recruitment and function of liver immune cells. However, the mechanism of liver EC injury and the occurrence of intercellular crosstalk in liver fibrosis are still unclear. In this study, C57BL/6 male mice were treated with CCl4 for 6 weeks to establish a liver fibrosis model. Masson staining and immunohistochemistry were performed to assess the extent of liver fibrosis. Liver endothelial injury was detected by using scanning electron microscopy (SEM) and PCR technology. Single-cell RNA sequencing (scRNA-seq) was performed to analyze phenotypic changes in nonparenchymal cells and dissect intercellular crosstalk in liver fibrosis. A total of 24,534 cells were analyzed and clustered into 10 main cell subsets. Liver ECs decreased significantly, and macrophage recruitment increased in the CCl4 group. The LSEC fenestrae and surface receptors expression were reduced, and the expression of Cd34 was upregulated. Liver ECs exhibited dense cellular crosstalk with immune cells such as macrophages, T cells, and B cells. The analysis of intercellular signaling pathways revealed that immune cells targeted liver ECs through the Ptprc-Mrc1 and Sell-Podxl signaling pathways to maintain intercellular interactions during liver fibrosis. We described the single-cell landscape of a liver fibrosis mouse model and demonstrated the presence of tight intracellular crosstalk between ECs with macrophages, T, and B cells, revealing cell-cell communications among liver immune cells-ECs during the process of liver fibrosis. The Ptprc-Mrc1 and Sell-Podxl signaling pathways exerted prominent roles in the interaction between immune cells and liver ECs.
Project description:Genes expression profile in liver macrophages isolated from wild type C57BL/6J mice fed either a high fat or normal diet for 18 weeks