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Evaluation of the immortalized primary human hepatocyte cell line Fa2N-4 as a model for MASLD

GSE324401 Homo sapiens (human) RNA-seq (gene expression) 48 samples Submitted 2026/03/15 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 48 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
48 samples: 12 conditions, mostly with about 4 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.
Summary (written by the submitters)
Background and aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease worldwide, yet preclinical in vitro models remain suboptimal. MASLD studies predominantly rely on hepatocellular carcinoma–derived cell lines, such as HepG2, which are poorly differentiated and exhibit cancer-associated metabolic reprogramming that suppresses key adult hepatic functions.
Read the full summary ↓
Primary human hepatocytes, on the other hand, offer greater physiological relevance, but their use is limited by cost, availability, donor variability, and rapid dedifferentiation. Here, we evaluated the immortalized primary human hepatocyte cell line Fa2N-4 as an alternative in vitro model for MASLD. Methods: We performed a comparative analysis of Fa2N-4 and HepG2 cells, assessing genomic architecture, lipid-induced steatosis, and pharmacological responsiveness. Results: The two models exhibited pronounced differences, including distinct karyotypes, divergent MASLD-associated genetic risk variant profiles, and markedly different transcriptional responses to lipid loading and drug treatment. We further examined the hepatic response to resmetirom, the first U.S. Food and Drug Administration (FDA) approved medication specifically for treating MASH. Resmetirom, a thyroid hormone receptor-β agonist, reduced intracellular triglyceride accumulation in Fa2N-4 cells, but not in HepG2 cells, and this was accompanied by induction of mitochondrial glycolysis and oxidative phosphorylation pathways. Conclusions: Together, these findings demonstrate that hepatocyte model selection critically influences experimental outcomes in MASLD research and highlight Fa2N-4 cells as a physiologically relevant platform for mechanistic and translational studies of MASLD therapeutics.
This dataset
Open GSE324401 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 GSE324401_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 PRJNA1435030 and SRA study SRP682537. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
12 conditions, mostly with about 4 replicates each
HepG2_NT ×4 HepG2_MASLD ×4 HepG2_SIM_Veh_RSM ×4 HepG2_SIM_RSM ×4 HepG2_SEQ_Veh_RSM ×4 HepG2_SEQ_RSM ×4 Fa2N4_NT ×4 Fa2N4_MASLD ×4 +4 more

Supports a between-group comparison across 48 samples.

How we read this: 12 replicated groups read from 48 sample titles; they account for 48 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

+ 8 more — browse all 48 samples with per-sample file links →

Datasets on a similar topic

Search all human RNA-seq datasets in GEO →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.