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Physiologically relevant media are associated with overlapping metabolic responses in primary human hepatocytes and Huh7 cells

GSE334407 Homo sapiens (human) RNA-seq (gene expression) 30 samples Submitted 2026/07/08 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 30 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
30 samples: 6 conditions, mostly with about 5 replicates eachGroups 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
Physiologically relevant media are associated with overlapping metabolic responses in primary human hepatocytes and Huh7 cellsPhysiological reports · 2026
Summary (written by the submitters)
Background and aims: The initiation and progression of metabolic dysfunction-associated steatotic liver disease (MASLD) is challenging to study in vivo in humans and robust in vitro high-fidelity disease models are limited. Although primary human hepatocytes (PHH) are often considered to be the gold-standard, immortalized hepatic cell lines are often utilised because of their scalability and experimental tractability.
Read the full summary ↓
Therefore, the aim of this study was to compare the metabolic responses of PHHs with our characterized Huh7-based model when exposed to the physiologically-relevant fatty acid (FA) mixtures. Methods: PHH and Huh7 cells were treated with 2% human serum and a combination of sugar and FAs enriched in either unsaturated (OPLA) or saturated (POLA) FAs for 4 or 7 days, respectively. Stable isotope tracers were utilized to investigate basal changes in hepatocyte metabolism in response to different treatment regimes. Changes in cell viability, media biochemistry, intracellular metabolism, lipid droplet morphology and gene expression were quantified. Results: Huh7 cells had greater viability than PHH, while NEFA uptake and triglyceride secretion were similar. Both OPLA and POLA increased the proportion of large lipid droplets in Huh7 cells, whereas only OPLA produced comparable effects in PHH. Despite higher baseline TG in PHH, both models showed similar lipid composition, de novo lipogenic responses, and glycogen levels. Compared to Huh7 cells PHH exhibited higher media 3-hydroxybutyrate, lower media lactate, reduced glucose uptake, and donor-dependent transcriptomic variability. Conclusions: Our data demonstrate that Huh7 cells are metabolically adaptable and when cultured in physiologically relevant media metabolic readouts are more similar to those observed in PHH cells, thus making Huh7 a potentially useful workhorse model to investigate relevant pathways that may underpin the development of MASLD.
Published in
Physiologically relevant media are associated with overlapping metabolic responses in primary human hepatocytes and Huh7 cells
Cross E, Westcott F, Smith K et al. · Physiological reports 2026 · PMID 42397153 · doi:10.14814/phy2.70989
This dataset
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.

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 GSE334407_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1474965 and SRA study SRP706907. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly with about 5 replicates each
Huh7 cells Control ×5 Huh7 cells OPLA ×5 Huh7 cells POLA ×5 PHH cells Control ×5 PHH cells OPLA ×5 PHH cells POLA ×5

Supports a between-group comparison across 30 samples.

How we read this: 6 replicated groups read from 30 sample titles; they account for 30 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
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