Single-cell RNA sequencing and functional analysis reveal the role of altered glycosylation levels of hepatic macrophages in liver cirrhosis.

Abstract

Background: Liver cirrhosis represents a critical stage of chronic liver disease, characterized by progressive liver damage, cellular dysfunction, and disrupted cell-to-cell interactions. Glycosylation, an essential post-translational modification, significantly influences cellular behavior and disease progression. Its role in cirrhosis at the single-cell level remains unclear, despite its importance.

Methods: This study, based on single-cell glycosylation and transcriptome data, compared the expression of differentially expressed genes in liver tissues from cirrhotic and healthy control samples, identifying changes in glycosylation-related genes and their functional pathway enrichment characteristics. Additionally, it analyzed the composition of immune cells and intercellular interaction features, with a focus on the interaction between macrophages and other immune cells and their potential role in immune regulation.

Results: The analysis revealed significant changes in immune cell composition and glycosylation patterns in cirrhotic livers. Specifically, the number of macrophages increased substantially, while overall glycosylation levels decreased. Enhanced interactions between macrophages and other cell types were observed, highlighting the central role of macrophages in reshaping the immune microenvironment during cirrhosis progression. Gene expression analysis showed a marked upregulation of FUCA1, a gene encoding a glycosylation-related hydrolase. This change was strongly associated with the observed reduction in glycosylation levels. Functional enrichment analysis further revealed that glycosylation-related genes were primarily involved in immune pathways, including antigen processing and presentation, cytokine signaling, and immune activation.

Conclusions: Single-cell glycosylation analysis provides crucial insights into immune cell interactions in cirrhosis. Targeting glycosylation pathways in macrophages may offer new treatment strategies for cirrhosis.