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

ABSTRACT:

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 cockt

SUBMITTER: Sanchez-Quant E 

PROVIDER: S-EPMC10583437 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature