ArticleArchives of toxicology2021
Comparing in vitro human liver models to in vivo human liver using RNA-Seq.
Article in Archives of toxicology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
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Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- A comprehensive transcriptomic comparison of hepatocyte model systems improves selection of models for experimental use.Communications biology · 2022Pooled it
- The in vitro alkaline comet assay with liver models as a complementary tool for genotoxicity assessment of N-nitrosamines.Archives of toxicology · 2026Article
- Systems biology framework for the rational design of operational conditions for in vitro/in vivo translation of tissue models.Science advances · 2026Article
- Systematic comparison of temporal hepatotoxicant-induced gene network responses across 3 liver test systems.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- FOXM1 inhibition primes terminal differentiation of human iPSC-derived hepatocytes.Cell death discovery · 2026Article
- Phenotypical and functional characterization of a HepG2 cell clone stably overexpressing cytochrome P450 (CYP) 2C9.BMC research notes · 2026Article
- Improving hepatic metabolic function with 3D iPSC-derived human hepatocytes.Cell biology and toxicology · 2026Article
- Single-cell transcriptomics of acetaminophen-induced responses in human 2D and 3D liver microtissues.Archives of toxicology · 2026Article
- Epithelial Reprogramming and Transition during Pulmonary Bioengineering.bioRxiv : the preprint server for biology · 2026Article
- Evaluation of in vitro liver models and non-human primates for predicting ADAR RNA editing efficiency in human liver.Scientific reports · 2025Article
- Nutrient environment improves drug metabolic activity in human iPSC-derived hepatocytes and HepG2.Archives of toxicology · 2025Article
- Application of Induced Pluripotent Stem Cells (iPSCs) in Hereditary and Viral Diseases of the Liver: Modeling and Treatment.International journal of molecular sciences · 2025Review
- Subfamily-selective PCR primers for the human LINE1 L1PA lineage.Scientific reports · 2025Article
- Liver-specific lncRNAs associated with liver cancers.FEBS open bio · 2025Review
- Glyoxalase-1 overexpression attenuates arterial wall stiffening in diabetic mice.Cardiovascular diabetology · 2025Article
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- Experimental Models to Investigate PNPLA3 in Liver Steatosis.Liver international : official journal of the International Association for the Study of the Liver · 2025Review
- Investigation on ABCC6-Deficient Human Hepatocytes Generated by CRISPR-Cas9 Genome Editing.Cells · 2025Article
- Computational modelling identifies primary mediators of crosstalk between DNA damage and oxidative stress responses.PLoS computational biology · 2025Article
Corrections and comments
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Authors and funding
24 authors at 9 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver plays an important role in xenobiotic metabolism and represents a primary target for toxic substances. Many different in vitro cell models have been developed in the past decades. In this study, we used RNA-sequencing (RNA-Seq) to analyze the following human in vitro liver cell models in comparison to human liver tissue: cancer-derived cell lines (HepG2, HepaRG 3D), induced pluripotent stem cell-derived hepatocyte-like cells (iPSC-HLCs), cancerous human liver-derived assays (hPCLiS, human precision cut liver slices), non-cancerous human liver-derived assays (PHH, primary human hepatocytes) and 3D liver microtissues. First, using CellNet, we analyzed whether these liver in vitro cell models were indeed classified as liver, based on their baseline expression profile and gene regulatory networks (GRN). More comprehensive analyses using non-differentially expressed genes (non-DEGs) and differential transcript usage (DTU) were applied to assess the coverage for important liver pathways. Through different analyses, we noticed that 3D liver microtissues exhibited a high similarity with in vivo liver, in terms of CellNet (C/T score: 0.98), non-DEGs (10,363) and pathway coverage (highest for 19 out of 20 liver specific pathways shown) at the beginning of the incubation period (0 h) followed by a decrease during long-term incubation for 168 and 336 h. PHH also showed a high degree of similarity with human liver tissue and allowed stable conditions for a short-term cultivation period of 24 h. Using the same metrics, HepG2 cells illustrated the lowest similarity (C/T: 0.51, non-DEGs: 5623, and pathways coverage: least for 7 out of 20) with human liver tissue. The HepG2 are widely used in hepatotoxicity studies, however, due to their lower similarity, they should be used with caution. HepaRG models, iPSC-HLCs, and hPCLiS ranged clearly behind microtissues and PHH but showed higher similarity to human liver tissue than HepG2 cells. In conclusion, this study offers a resource of RNA-Seq data of several biological replicates of human liver cell models in vitro compared to human liver tissue.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.