ArticleNature communications2020
Amino acid levels determine metabolism and CYP450 function of hepatocytes and hepatoma cell lines.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 125 citations in OpenAlex.
- A comprehensive transcriptomic comparison of hepatocyte model systems improves selection of models for experimental use.Communications biology · 2022Pooled it
- Human serum-supplemented cell culture conditions improve xenobiotic metabolism in hepatoma cell lines HepG2 and Huh7.Archives of toxicology · 2026Article
- Six-compound cocktail for maturation of human pluripotent stem cell-derived liver spheroids for toxicity prediction.Nature communications · 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
- Glycine: The missing link between carbohydrate and xenobiotic metabolism in the maturing human hepatocyte.iScience · 2026Article
- A DPHV-liver module recapitulates AML infiltration and chemotherapy-induced hepatotoxicity with translational utility.Science advances · 2026Article
- Improving hepatic metabolic function with 3D iPSC-derived human hepatocytes.Cell biology and toxicology · 2026Article
- A multi-omic approach reveals iron availability influences cell fate fidelity.npj metabolic health and disease · 2026Article
- A broad kinase inhibitor library live cell imaging screen using liver, kidney and cardiac hiPSC-ICAM1-eGFP reporter lineages identifies liabilities for TNFα pathway modulation.Archives of toxicology · 2026Article
- Article
- Antibiotic exposure exacerbates acute-on-chronic liver failure via gut microbiota imbalance and secondary liver lesion.Journal of medical microbiology · 2026Article
- Cysteine Restriction Induces Ferroptosis Depending on theGastro hep advances · 2026Article
- Nutrient environment improves drug metabolic activity in human iPSC-derived hepatocytes and HepG2.Archives of toxicology · 2025Article
- Real-Time Untargeted Monitoring of Intracellular Metabolism in Live Cells UsingJournal of the American Chemical Society · 2025Article
- Biochemical and Biophysical Properties of Extracellular Matrix Nanofibers Modulate iPSC-Derived Human Hepatocyte Maturation.Journal of biomedical materials research. Part A · 2025Article
- Article
- In vitro-in silico analysis reveals that loss of tankyrase1/2 improves bile acid handling in genetically engineered HepG2 cultures.Archives of toxicology · 2025Article
- Altered metabolic profiles in colon and rectal cancer.Scientific reports · 2025Article
- Induced pluripotent stem cell-derived mesenchymal stem cells for modeling and treating metabolic associated fatty liver disease and metabolic associated steatohepatitis: Challenges and opportunities.World journal of stem cells · 2025Review
- Amino Acid Hepatotoxicity Biomarkers in Human Hepatic Organoids: Promising Standardization of Drug Toxicity Evaluation.ACS pharmacology & translational science · 2025Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 9 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Predicting drug-induced liver injury in a preclinical setting remains challenging, as cultured primary human hepatocytes (PHHs), pluripotent stem cell-derived hepatocyte-like cells (HLCs), and hepatoma cells exhibit poor drug biotransformation capacity. We here demonstrate that hepatic functionality depends more on cellular metabolism and extracellular nutrients than on developmental regulators. Specifically, we demonstrate that increasing extracellular amino acids beyond the nutritional need of HLCs and HepG2 cells induces glucose independence, mitochondrial function, and the acquisition of a transcriptional profile that is closer to PHHs. Moreover, we show that these high levels of amino acids are sufficient to drive HLC and HepG2 drug biotransformation and liver-toxin sensitivity to levels similar to those in PHHs. In conclusion, we provide data indicating that extracellular nutrient levels represent a major determinant of cellular maturity and can be utilized to guide stem cell differentiation to the hepatic lineage.
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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.