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Updated: Jun 14, 2025
Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
Spatial Transcriptomics Reveals the Transcriptomic Signatures in a Mouse Model of Pediatric Metabolic
Lu Jiang1, Qing-Yang Xu2, Yong-Chang Zhou3
1Division of Pediatric Gastroenterology and Nutrition, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Institute for Pediatric Research, Shanghai, China; Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
Insights
A new mouse model mimics pediatric metabolic dysfunction-associated steatohepatitis (MASH), showing key disease features. This model highlights increased cytochrome P450 2E1, potentially linking it to MASH development in children.
Area of Science:
- Hepatology
- Pediatric Gastroenterology
- Molecular Biology
Background:
- Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease and a leading cause of chronic liver disease in children.
- The pathogenesis of pediatric MASH is poorly understood due to a lack of suitable animal models.
Purpose of the Study:
- To develop and characterize a mouse model for pediatric MASH.
- To investigate the hepatic transcriptomic profile of this model using spatial transcriptomics.
Main Methods:
- C57BL/6J mice were fed a Western diet (WD) with weekly carbon tetrachloride (CCl4) injections from 3 to 8 weeks of age.
- Histological analysis and spatial transcriptomics were performed on liver tissues.
- Gene expression analysis focused on identifying key markers and pathways.
Main Results:
- The WD + CCl4 model induced liver steatosis, portal inflammation, and fibrosis, mirroring human pediatric MASH (Type 2).
- Spatial transcriptomics identified a cluster enriched in lipid metabolism pathways.
- Cytochrome P450 2E1 was identified as a top marker gene, upregulated in the periportal area.
Conclusions:
- The developed mouse model accurately reflects the histological features of human pediatric MASH.
- Upregulation of cytochrome P450 2E1 in the periportal region may play a role in pediatric MASH pathogenesis.
Abstract:
Metabolic dysfunction-associated steatohepatitis (MASH) is considered the progressive form of metabolic dysfunction-associated steatotic liver disease, which is the leading cause of chronic liver disease in children. However, the pathogenesis of pediatric MASH remains poorly understood because of the lack of animal models. In this study, a mouse model of pediatric MASH was developed and its hepatic transcriptomic profile was characterized using spatial transcriptomics technology. C57BL/6J mice were fed a Western diet (WD) along with weekly injections of carbon tetrachloride (CCl4) from the age of 3 weeks and lasting up to 8 weeks. After 5 weeks of feeding, WD + CCl4-treated mice showed significant liver injury without the development of insulin resistance. Histologically, WD + CCl4 induced key features of type 2 MASH, the most common type observed in children, characterized by liver steatosis, portal inflammation, and portal fibrosis. Spatial transcriptomics analysis of liver tissues indicated that cluster 0 in the mouse from the WD + CCl4 group was enriched in pathways associated with lipid metabolism. Further investigation revealed that cytochrome p450 2E1 was the top marker gene of cluster 0, and its expression was increased in the periportal area of mice from the WD + CCl4 group. These findings suggest that this mouse model of pediatric MASH mirrors the histologic features of human MASH, and the up-regulation of cytochrome p450 2E1 may be linked to the disease pathogenesis.
