ArticleGenome biology2023
Single-cell metabolic profiling reveals subgroups of primary human hepatocytes with heterogeneous responses to drug challenge.
Article in Genome biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- JMJD3-mediated HADH demethylation orchestrates hepatocyte maturation through fatty acid β-oxidation-dependent histone acetylation.Experimental & molecular medicine · 2026Article
- Multi-Omics-Guided Design and Safety Engineering of Nucleic Acid Therapeutics: From Molecular Perturbation to Predictive Toxicology and Precision Translation.Chemical biology & drug design · 2026Review
- Visualization of CYP3A4 expression at both mRNA and protein levels simultaneously at single cell resolution in various conditions using RNAscope combined with immunofluorescence.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Chromatin dynamics and regulatory drivers of hypoplastic hepatic progenitor cells in partial hepatectomy model.Communications biology · 2025Article
- A Review on New Frontiers in Drug-Drug Interaction Predictions and Safety Evaluations with In Vitro Cellular Models.Pharmaceutics · 2025Review
- Influence of a Zombie-like State of the Liver on Drugs and Its Medico-Legal Implications: A Scoping Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Single-cell metabolic profiling reveals subgroups of primary human hepatocytes with heterogeneous responses to drug challenge.Genome biology · 2023Article
- Human induced pluripotent stem cell-derived liver-on-a-chip for studying drug metabolism: the challenge of the cytochrome P450 family.Frontiers in pharmacology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundXenobiotics are primarily metabolized by hepatocytes in the liver, and primary human hepatocytes are the gold standard model for the assessment of drug efficacy, safety, and toxicity in the early phases of drug development. Recent advances in single-cell genomics demonstrate liver zonation and ploidy as main drivers of cellular heterogeneity. However, little is known about the impact of hepatocyte specialization on liver function upon metabolic challenge, including hepatic metabolism, detoxification, and protein synthesis.
resultsHere, we investigate the metabolic capacity of individual human hepatocytes in vitro. We assess how chronic accumulation of lipids enhances cellular heterogeneity and impairs the metabolisms of drugs. Using a phenotyping five-probe cocktail, we identify four functional subgroups of hepatocytes responding differently to drug challenge and fatty acid accumulation. These four subgroups display differential gene expression profiles upon cocktail treatment and xenobiotic metabolism-related specialization. Notably, intracellular fat accumulation leads to increased transcriptional variability and diminishes the drug-related metabolic capacity of hepatocytes.
conclusionsOur results demonstrate that, upon a metabolic challenge such as exposure to drugs or intracellular fat accumulation, hepatocyte subgroups display different and heterogeneous transcriptional responses.
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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 Socratic graph.