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Omics · study · 2026

Comparable Transcriptomic Profiles of HepaRG and HuH7 Cells Cultured in Chemically Defined and Serum-Based Media Using Primary Human Hepatocytes as Reference

Listed in NCBI GEO

The composition of culture medium is a major, yet frequently undercontrolled, determinant of hepatic cell state in vitro.

Description

For decades, fetal bovine serum (FBS) has been routinely incorporated into liver cell culture. Its undefined and lot-to-lot variable composition can, however, confound cell identity and experimental reproducibility.

Serum-free, chemically defined media (CDM) represent an alternative approach that can improve standardization, but the consequences of transitioning from FBS-supplemented media (FBS-SM) to CDM remain insufficiently characterized in hepatic models, particularly with respect to metabolic and detoxification programs that govern xenobiotic handling and hepatotoxicity readouts. Here, we systematically assessed how replacing FBS-SM with CDM remodels transcriptomic profiles in two widely used human hepatic cell lines (HepaRG and HuH7 cells) and compared the results to that obtained in primary human hepatocytes (PHH).

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Global transcriptomic analyses indicated that cell type was the primary driver of variance, whereas medium induced a model-dependent secondary effect. Functional interpretation showed preferential enhancement of xenobiotic metabolism and transport-associated programs in HepaRG cells, while HuH7 cells responses were dominated by lipid/sterol homeostasis and stress-linked processes. Benchmarking against PHH based on hepatic identity and detoxification gene panels further supported improved PHH alignment for HepaRG cells under CDM compared to cultures with FBS-SM, with limited improvement for HuH7 cells.

Collectively, these findings address a key knowledge gap by defining how FBS-SM and CDM impact the transcriptomic profiles of HepaRG and HuH7 cells.

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access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[organism].NCBITaxon:9606source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title