PuSH - Publication Server of Helmholtz Zentrum München: Single-cell metabolic profiling reveals subgroups of primary human hepatocytes with heterogeneous responses to drug challenge.

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... Journal

... Publication Type

... Research Data

... Publication Year

Publication overview

Support & Contact

Contact persons

Help

Data protection

Sánchez Quant, E.S. ; Richter, M. ; Colomé-Tatché, M. ; Martinez Jimenez, C.P.

Single-cell metabolic profiling reveals subgroups of primary human hepatocytes with heterogeneous responses to drug challenge.

Genome Biol. 24:234 (2023)

Publ. Version/Full Text

DOI

PMC

	Open Access Gold

Abstract
Metrics
Extra information

BACKGROUND: Xenobiotics 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. RESULTS: Here, 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. CONCLUSIONS: Our results demonstrate that, upon a metabolic challenge such as exposure to drugs or intracellular fat accumulation, hepatocyte subgroups display different and heterogeneous transcriptional responses.

Altmetric

Additional Metrics?

[➜Log in]

Edit extra informations Login

Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Cytochrome P450 ; Dili ; Drug Metabolism ; Hepatic Steatosis ; Lipid Metabolism ; Liver ; Nafld ; Primary Human Hepatocytes ; Single-cell Transcriptomics; Fatty Liver-disease; Gene-expression; Transcriptional Regulation; Cytochrome-p450 Probes; Hepatic Steatosis; Enzymes; Cocktail; Mechanisms; Midazolam; Risk

ISSN (print) / ISBN 1474-760X

e-ISSN 1465-6906

Journal Genome Biology

Quellenangaben Volume: 24, Issue: 1, Article Number: 234

Publisher BioMed Central

Publishing Place Campus, 4 Crinan St, London N1 9xw, England

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Helmholtz Pioneer Campus (HPC)
Institute of Computational Biology (ICB)

Grants Impuls-und Vernetzungsfonds of the Helmholtz-Gemeinschaft
C.P.M-J at the Helmholtz Pioneer Campus
Projekt DEAL