GEO series

Hepatocyte-specific PPARγ Deletion Uncovers Role of an Antagonistic PPARγ–HNF4α Transcriptional Axis in MASLD Progression

GSE328680 Mus musculus (mouse) Single-nucleus RNA-seq 12 samples Submitted 2026/04/22 Platform GPL34290

At a glance

Single-nucleus RNA-seq · mouse · 12 samples

What it is: Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism: Mus musculus (mouse)
Samples: 12 samples: 3 × WT, 2 months FFD, repeat vs 3 × PPARG KO, 2 months FFD, repeat vs 3 × WT, 5 months FFD, repeat vs 3 × PPARG KO, 5 months FFD, repeatGroups 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: Hepatocyte-specific PPARγ Deletion Uncovers Role of an Antagonistic PPARγ-HNF4α Transcriptional Axis in Metabolic Dysfunction-Associated Steatotic Liver Disease ProgressionThe American journal of pathology · 2026

Summary (written by the submitters)

Systemic PPARγ agonist therapies have been investigated for clinical use in MASLD. Previous studies, however, have shown that PPARγ activation in hepatocytes worsens MASLD. Overall, the precise molecular mechanisms regulated by PPARγ in hepatocyte during MASLD remain incompletely defined. Hepatocyte-specific PPARγ knockout mice were fed a clinically-relevant fast-food diet (FFD) for 2 or 5-months to characterize the role of PPARγ in MASLD progression.

Read the full summary ↓

PPARγ expression and activity were increased in murine FFD-model and in hepatocytes of human MASLD/MASH patients, based on single-nucleus RNA-sequencing analysis. PPARγ-deletion conferred protection against diet-induced steatosis, fibrosis, and liver injury by suppressing lipogenic, inflammatory, and fibrogenic signaling. Although de-novo fatty-acid synthesis was only modestly affected and compensated with disease progression, enhancement of lipolysis and suppression of lipid droplet stabilization machinery was persistent. PPARγ-deletion robustly inhibited expression and signaling-activity of TGFβ1, a master regulator of hepatic ¬fibrosis, throughout the progression of MASLD. Importantly, a novel PPARγ-HNF4α regulatory axis in MASLD was identified, with increased HNF4α mRNA/protein expression and activation of its downstream metabolic networks in PPARγ-deficient livers. Further, integration of ChIP-seq and transcriptomic analysis revealed that HNF4α might be co-regulating a major fraction (>70%) of genes under direct control of PPARγ during MASLD. This study provides a comprehensive temporal framework for hepatocyte PPARγ function in MASLD, revealing an antagonistic PPARγ-HNF4α transcriptional network that governs hepatic metabolic fate.

Published in

Hepatocyte-specific PPARγ Deletion Uncovers Role of an Antagonistic PPARγ-HNF4α Transcriptional Axis in Metabolic Dysfunction-Associated Steatotic Liver Disease Progression

Bano S, Copeland MA, Liu JJ et al. · The American journal of pathology 2026 · PMID 42119808 · doi:10.1016/j.ajpath.2026.04.015

This dataset

Open GSE328680 in finder → Find more mouse 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 GSE328680_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1456111 and SRA study SRP693625. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42119808) ↗

Study design

3 × WT, 2 months FFD, repeat vs 3 × PPARG KO, 2 months FFD, repeat vs 3 × WT, 5 months FFD, repeat vs 3 × PPARG KO, 5 months FFD, repeat

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 12 sample titles; they account for 12 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

GSM9687124 WT, 2 months FFD, repeat 1 WT, 2 months FFD, repeat
GSM9687125 WT, 2 months FFD, repeat 2 WT, 2 months FFD, repeat
GSM9687126 WT, 2 months FFD, repeat 3 WT, 2 months FFD, repeat
GSM9687127 PPARG KO, 2 months FFD, repeat 1 PPARG KO, 2 months FFD,…
GSM9687128 PPARG KO, 2 months FFD, repeat 2 PPARG KO, 2 months FFD,…
GSM9687129 PPARG KO, 2 months FFD, repeat 3 PPARG KO, 2 months FFD,…
GSM9687130 WT, 5 months FFD, repeat 1 WT, 5 months FFD, repeat
GSM9687131 WT, 5 months FFD, repeat 2 WT, 5 months FFD, repeat
GSM9687132 WT, 5 months FFD, repeat 3 WT, 5 months FFD, repeat
GSM9687133 PPARG KO, 5 months FFD, repeat 1 PPARG KO, 5 months FFD,…
GSM9687134 PPARG KO, 5 months FFD, repeat 2 PPARG KO, 5 months FFD,…
GSM9687135 PPARG KO, 5 months FFD, repeat 3 PPARG KO, 5 months FFD,…

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GSE14921 Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism 6 samples shares hepatocyte-specific, deletion

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