GEO series

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

GSE324107 Homo sapiens (human) RNA-seq (gene expression) 20 samples Submitted 2026/07/21 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 20 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Homo sapiens (human)
Samples: 20 samples: 7 conditions, mostly in triplicateGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.
Paper: Cell line identity rather than medium composition determines transcriptomic profiles of HepaRG and HuH7 cells cultured in chemically defined or serum-based media: comparison with primary human hepatocytesArchives of toxicology · 2026

Summary (written by the submitters)

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

Read the full summary ↓

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). 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.

Published in

Cell line identity rather than medium composition determines transcriptomic profiles of HepaRG and HuH7 cells cultured in chemically defined or serum-based media: comparison with primary human hepatocytes

Ali ASM, Sprenger H, Braeuning A et al. · Archives of toxicology 2026 · PMID 42446672 · doi:10.1007/s00204-026-04502-z

This dataset

Open GSE324107 in finder → Find more human RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE324107_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1433437 and SRA study SRP681710. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42446672) ↗

Study design

7 conditions, mostly in triplicate

HepaRG, CDM, ×3 HepaRG, FBS-SM, ×3 HuH7, CDM, ×3 HuH7, FBS-SM, ×3 HeLa, CDM, ×3 HeLa, FBS-SM, ×3 Pooled primary human hepatocytes, ×2

Supports a between-group comparison across 20 samples.

How we read this: 7 replicated groups read from 20 sample titles; they account for 20 of them. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

GSM9568319 HepaRG, CDM, biological replicate 1 HepaRG, CDM,
GSM9568320 HepaRG, CDM, biological replicate 2 HepaRG, CDM,
GSM9568321 HepaRG, CDM, biological replicate 3 HepaRG, CDM,
GSM9568322 HepaRG, FBS-SM, biological replicate 1 HepaRG, FBS-SM,
GSM9568323 HepaRG, FBS-SM, biological replicate 2 HepaRG, FBS-SM,
GSM9568324 HepaRG, FBS-SM, biological replicate 3 HepaRG, FBS-SM,
GSM9568325 HuH7, CDM, biological replicate 1 HuH7, CDM,
GSM9568326 HuH7, CDM, biological replicate 2 HuH7, CDM,
GSM9568327 HuH7, CDM, biological replicate 3 HuH7, CDM,
GSM9568328 HuH7, FBS-SM, biological replicate 1 HuH7, FBS-SM,
GSM9568329 HuH7, FBS-SM, biological replicate 2 HuH7, FBS-SM,
GSM9568330 HuH7, FBS-SM, biological replicate 3 HuH7, FBS-SM,
GSM9568331 Pooled primary human hepatocytes, replicate 1 Pooled primary human he…
GSM9568332 Pooled primary human hepatocytes, replicate 2 Pooled primary human he…
GSM9568333 HeLa, CDM, biological replicate 1 HeLa, CDM,
GSM9568334 HeLa, CDM, biological replicate 2 HeLa, CDM,
GSM9568335 HeLa, CDM, biological replicate 3 HeLa, CDM,
GSM9568336 HeLa, FBS-SM, biological replicate 1 HeLa, FBS-SM,
GSM9568337 HeLa, FBS-SM, biological replicate 2 HeLa, FBS-SM,
GSM9568338 HeLa, FBS-SM, biological replicate 3 HeLa, FBS-SM,

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