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Comparing in vitro human liver models to in vivo human liver using RNA-Seq
Rajinder Gupta1, Yannick Schrooders1, Duncan Hauser1
1Department of Toxicogenomics, School of Oncology and Developmental Biology (GROW), Maastricht University, Maastricht, The Netherlands.
Archives of Toxicology
|October 27, 2020
Summary
3D liver microtissues and primary human hepatocytes (PHH) closely resemble human liver tissue for xenobiotic metabolism studies. Cancer-derived HepG2 cells show the lowest similarity, requiring cautious use in hepatotoxicity research.
Area of Science:
- Hepatology and Toxicology
- Genomics and Transcriptomics
- In Vitro Modeling
Background:
- The liver is crucial for xenobiotic metabolism and a key target for toxins.
- Various human in vitro liver cell models exist, but their fidelity to in vivo tissue varies.
- Accurate in vitro models are essential for reliable hepatotoxicity assessments.
Purpose of the Study:
- To compare the similarity of multiple human in vitro liver cell models to human liver tissue using RNA-sequencing (RNA-Seq).
- To evaluate different liver cell models for their suitability in xenobiotic metabolism and hepatotoxicity studies.
- To provide a comprehensive RNA-Seq data resource for various liver in vitro models.
Main Methods:
- RNA-sequencing (RNA-Seq) was performed on several human in vitro liver models and human liver tissue.
- CellNet analysis assessed model classification and gene regulatory network (GRN) similarity.
- Non-differentially expressed genes (non-DEGs) and differential transcript usage (DTU) analyses evaluated pathway coverage.
Main Results:
- 3D liver microtissues demonstrated the highest similarity to human liver tissue at baseline (CellNet C/T score: 0.98).
- Primary human hepatocytes (PHH) showed high similarity and supported stable short-term cultures (24h).
- HepG2 cancer-derived cells exhibited the lowest similarity (CellNet C/T score: 0.51), indicating potential limitations for hepatotoxicity studies.
Conclusions:
- 3D liver microtissues and PHH are promising in vitro models for liver research, closely mimicking in vivo human liver.
- HepG2 cells, while widely used, show significant differences from human liver tissue and should be used cautiously.
- This study provides valuable RNA-Seq data to guide the selection of appropriate in vitro liver models for toxicological research.
