Open AccessArticle
Single-Cell Transcriptomic Analysis of Different Liver Fibrosis Models: Elucidating Molecular Distinctions and Commonalities
by
Guofei Deng, Xiaomei Liang, Yuxi Pan, Yusheng Luo, Zizhen Luo, Shaoxuan He, Shuai Huang, Zhaopeng Chen, Jiancheng Wang and Shuo Fang
Biomedicines 2025, 13(8), 1788; https://doi.org/10.3390/biomedicines13081788 (registering DOI) - 22 Jul 2025
Abstract
Background: Liver fibrosis, a consequence of various chronic liver diseases, is characterized by excessive accumulation of extracellular matrix (ECM), leading to impaired liver function and potentially progressing to cirrhosis or hepatocellular carcinoma. The molecular mechanisms underlying liver fibrosis are complex and not
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Background: Liver fibrosis, a consequence of various chronic liver diseases, is characterized by excessive accumulation of extracellular matrix (ECM), leading to impaired liver function and potentially progressing to cirrhosis or hepatocellular carcinoma. The molecular mechanisms underlying liver fibrosis are complex and not fully understood. In vivo experiments are essential for studying the molecular mechanisms of the disease. However, the diverse principles behind mouse modeling techniques for liver fibrosis can complicate the elucidation of specific fibrotic mechanisms.
Methods: Five distinct liver fibrosis models were utilized: CONTROL, NASH (non-alcoholic steatohepatitis), BDL (bile duct ligation), TAA (thioacetamide), and CCl
4 (carbon tetrachloride). Patents for these drugs were reviewed using Patentscope
® and Worldwide Espacenet
®. ScRNA-seq was performed to analyze and compare the cellular and molecular differences in these models.
Results: The analysis revealed that, particularly in the drug-induced fibrosis models, hepatic stellate cells (HSCs), Kupffer cells, and T-cell subsets exhibit distinct regulatory patterns and dynamic remodeling processes across different liver fibrosis models. These findings highlight the heterogeneity of immune responses and extracellular matrix (ECM) remodeling in various models, providing important insights into the complex mechanisms underlying liver fibrosis.
Conclusions: The study enhances our understanding of liver fibrosis development and provides valuable insights for selecting the most representative animal models in future research. This comprehensive analysis underscores the importance of model-specific immune responses and ECM remodeling in liver fibrosis.
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