ArticleHepatology (Baltimore, Md.)2013
Proteome-wide analyses of human hepatocytes during differentiation and dedifferentiation.
Article in Hepatology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 129 citations in OpenAlex.
- Plasminogen as a prognostic biomarker for HBV-related acute-on-chronic liver failure.The Journal of clinical investigation · 2020Trial
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- Three-dimensional organoid culture enhances functional maturation of human pluripotent stem cell-derived hepatocytes.Molecular biology reports · 2026Article
- PAR3-mediated coordination of hepatocyte proliferation, maturation, and architecture in liver development and regeneration.Nature communications · 2026Article
- Hepatocyte Models for Metabolic Dysfunction-Associated Steatotic Liver Disease: A Comparative Analysis of Non-HepG2 Cell Models.International journal of molecular sciences · 2026Review
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- Advancing hepatotoxicity assessment: current advances and future directions.Toxicological research · 2025Review
- Standard Protocols for Characterising Primary and In Vitro-Generated Human Hepatocytes.Journal of cellular and molecular medicine · 2025Review
- Variable expression of hepatic genes in different liver tumor cell lines: conclusions for drug testing.Frontiers in cell and developmental biology · 2025Article
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- Efficient hepatocyte differentiation of primary human hepatocyte-derived organoids using three dimensional nanofibers (HYDROX) and their possible application in hepatotoxicity research.Scientific reports · 2024Article
- Review
- Activated hepatic stellate cell-derived Bmp-1 induces liver fibrosis via mediating hepatocyte epithelial-mesenchymal transition.Cell death & disease · 2024Article
- A Review of CYP-Mediated Drug Interactions: Mechanisms and In Vitro Drug-Drug Interaction Assessment.Biomolecules · 2024Review
- Liver three-dimensional cellular models for high-throughput chemical testing.Cell reports methods · 2023Review
- A strategy can be used to analyze intracellular interaction proteomics of cell-surface receptors.Amino acids · 2023Article
- Physiomimetic In Vitro Human Models for Viral Infection in the Liver.Seminars in liver disease · 2023Review
- Illuminating HBV with multi-scale modeling.Frontiers in systems biology · 2023Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
unlabelledFailure to predict hepatotoxic drugs in preclinical testing makes it imperative to develop better liver models with a stable phenotype in culture. Stem cell-derived models offer promise, with differentiated hepatocyte-like cells currently considered to be "fetal-like" in their maturity. However, this judgment is based on limited biomarkers or transcripts and lacks the required proteomic datasets that directly compare fetal and adult hepatocytes. Here, we quantitatively compare the proteomes of human fetal liver, adult hepatocytes, and the HepG2 cell line. In addition, we investigate the proteome changes in human fetal and adult hepatocytes when cultured in a new air-liquid interface format compared to conventional submerged extracellular matrix sandwich culture. From albumin and urea secretion, and luciferase-based cytochrome P450 activity, adult hepatocytes were viable in either culture model over 2 weeks. The function of fetal cells was better maintained in the air-liquid interface system. Strikingly, the proteome was qualitatively similar across all samples but hierarchical clustering showed that each sample type had a distinct quantitative profile. HepG2 cells more closely resembled fetal than adult hepatocytes. Furthermore, clustering showed that primary adult hepatocytes cultured at the air-liquid interface retained a proteome that more closely mimicked their fresh counterparts than conventional culture, which acquired myofibroblast features. Principal component analysis extended these findings and identified a simple set of proteins, including cytochrome P450 2A6, glutathione S transferase P, and alcohol dehydrogenases as specialized indicators of hepatocyte differentiation.
conclusionOur quantitative datasets are the first that directly compare multiple human liver cells, define a model for enhanced maintenance of the hepatocyte proteome in culture, and provide a new protein "toolkit" for determining human hepatocyte maturity in cultured cells.
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Registered trials
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 OpenQuestion graph.