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Updated: Jun 24, 2025
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Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
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Single-cell transcriptomics reveal the microenvironment landscape of perfluorooctane sulfonate-induced liver injury
Xinrong He1, Zhichao Sun1, Jingyuan Sun1
1Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
The Science of the Total Environment
|June 2, 2024
Summary
Perfluoroalkyl and polyfluoroalkyl substances (PFASs) cause liver injury, particularly in females. This study used single-cell RNA sequencing to reveal PFOS-induced changes in the female mouse liver microenvironment, identifying altered immune cells and fibroblast populations.
Area of Science:
- Toxicology and Environmental Health
- Hepatology
- Immunology
- Single-cell Omics
Background:
- Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are linked to liver injury in epidemiological and animal studies.
- The specific impact of PFASs on the liver's microenvironment, especially at the cellular level, remains poorly understood.
- Perfluorooctane sulfonic acid (PFOS) is a prevalent PFAS with known hepatotoxic effects.
Purpose of the Study:
- To investigate the effects of PFOS exposure on the hepatic microenvironment using a mouse model.
- To characterize cellular and molecular changes in the liver following PFOS administration, with a focus on female mice.
- To provide a single-cell level understanding of PFOS-induced liver injury.
Main Methods:
- Establishment of PFOS-induced liver injury models in male and female C57BL/6 mice via oral administration for 4 weeks.
- Hematoxylin and eosin staining for histological assessment of liver damage.
- Serum biochemical analysis to measure liver injury markers (ALT, AST).
- Single-cell RNA sequencing (scRNA-seq) on livers from PFOS-treated female mice to profile cellular composition and gene expression.
Main Results:
- PFOS exposure induced significant liver injury in both male and female mice, evidenced by elevated serum aminotransferases.
- Female mice displayed more severe liver injury compared to male mice.
- scRNA-seq analysis of female mouse livers revealed altered immune cell populations (upregulated dendritic cells and macrophages, downregulated T cells) and enriched hepatic stellate cells.
- Key ligand-receptor interactions between fibroblasts and endothelial cells (e.g., Dpp4_Cxcl12, Flt1_complex_Vegfa) were identified, suggesting roles in cell migration and angiogenesis.
Conclusions:
- PFOS exposure significantly alters the hepatic microenvironment in female mice, characterized by immune cell dysregulation and fibroblast activation.
- The identified cellular and molecular changes provide insights into the mechanisms underlying PFOS-induced liver injury.
- This study establishes a single-cell framework for understanding PFAS-related hepatic pathology.
