Wen Chunmei, Tao Huihui, Chen Huaizhou, Pu Wenjun, Yan Qiang, Zou Yaoshuang, Su Sheng Sean, Zhou Lingling, Peng Yali, Wang Guoying, Xu Tiantian, Zheng Xuejia, Wu Mengyao, Dai Yong
School of Medicine, Anhui University of Science & Technology, Huainan, China.
Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety of Anhui Higher Education Institutes, Huainan, China.
J Gastroenterol. 2025 May;60(5):607-620. doi: 10.1007/s00535-025-02218-y. Epub 2025 Jan 31.
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.
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.
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.
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.
肝硬化是慢性肝病的关键阶段，其特征为进行性肝损伤、细胞功能障碍以及细胞间相互作用紊乱。糖基化作为一种重要的翻译后修饰，显著影响细胞行为和疾病进展。尽管其具有重要性，但其在单细胞水平上在肝硬化中的作用仍不清楚。
本研究基于单细胞糖基化和转录组数据，比较了肝硬化样本和健康对照样本肝脏组织中差异表达基因的表达情况，确定了糖基化相关基因的变化及其功能通路富集特征。此外，分析了免疫细胞组成和细胞间相互作用特征，重点关注巨噬细胞与其他免疫细胞之间的相互作用及其在免疫调节中的潜在作用。
分析揭示了肝硬化肝脏中免疫细胞组成和糖基化模式的显著变化。具体而言，巨噬细胞数量大幅增加，而总体糖基化水平下降。观察到巨噬细胞与其他细胞类型之间的相互作用增强，突出了巨噬细胞在肝硬化进展过程中重塑免疫微环境的核心作用。基因表达分析显示，编码糖基化相关水解酶的基因FUCA1显著上调。这一变化与观察到的糖基化水平降低密切相关。功能富集分析进一步表明，糖基化相关基因主要参与免疫途径，包括抗原加工和呈递、细胞因子信号传导和免疫激活。
单细胞糖基化分析为肝硬化中免疫细胞相互作用提供了关键见解。针对巨噬细胞中的糖基化途径可能为肝硬化提供新的治疗策略。
