Abstract

In this study, we investigated the gene expression changes of liver sinusoidal endothelial cell and kupffer cell in healthy and cirrhotic states of the liver using single-cell ribonucleic acid sequencing data from more than 60 000 hepatic cells from five human healthy liver samples and five human cirrhotic liver samples, and further explored the roles of liver sinusoidal endothelial cell and kupffer cell in cirrhotic livers. We constructed the relevant signaling pathways for the interaction between liver sinusoidal endothelial cell and kupffer cell in healthy and cirrhotic livers based on the CellChat algorithm and revealed the possible pathogenic mechanism of such interactions in cirrhosis. Results showed that the cell numbers of both liver sinusoidal endothelial cell and kupffer cell were significantly reduced in cirrhotic livers compared to healthy livers. Genes associated with antigen processing and presentation and immune response (CTSL, CTSB, LGMN, HSPA1A, JUN, and CLEC1B, etc.) were down-regulated in liver sinusoidal endothelial cell from cirrhotic livers, suggesting that the immune function of liver sinusoidal endothelial cell from cirrhotic livers was impaired; genes associated with cellular senescence, apoptosis, programmed necrosis and tumor necrosis factor signaling pathway (CTSH, EDN1, IL1R1, CXCL2 and IGFBP3, etc.) were up-regulated in liver sinusoidal endothelial cell from cirrhotic livers, suggesting that liver sinusoidal endothelial cell was impaired, which resulted in a significant reduction in its cellular population. This study provides a new perspective for a deeper understanding of the roles and interactions between liver sinusoidal endothelial cell and kupffer cell in cirrhosis, and offers potential targets for the development of new therapeutic approaches.