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A Microphysiological Model of Human MASLD Reveals Paradoxical Response to Resmetirom

GSE313774 Homo sapiens (human) RNA-seq (gene expression) 33 samples Submitted 2025/12/15 Platform GPL20301
At a glance

RNA-seq (gene expression) · human · 33 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
33 samples: 33 × NG-A0648Groups 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
A microphysiological model of human MASLD reveals paradoxical response to resmetiromCommunications biology · 2026
Summary (written by the submitters)
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic disease with multiple etiologies, stemming from the interplay between local and systemic genetic, diet, and gene-environment interactions. To understand the progression of MASLD in a controlled setting, we utilized a human liver microphysiological system (MPS) to establish a physiologically relevant metabolic baseline and probe how primary human hepatocytes respond to perturbations in insulin, glucose, and free fatty acids (FFAs).
Read the full summary ↓
Replicate liver MPS were maintained in media with either 200 pM or 800 pM insulin for up to 3 weeks alone and in combination with standard glucose (5.5 mM), hyperglycemia (11 mM glucose), normal (20µM) and elevated FFA (100 µM). Together, hyperinsulinemia along with elevated glucose and FFAs, induces the release of pro-inflammatory chemokines, accumulation of triglycerides, and predisposes hepatocytes to insulin resistance. Treatment with the thyroid receptor ß agonist resmetirom normalizes hepatic fat content and partially rescues insulin sensitivity, but paradoxically induces higher CXCL1 and IL8 expression in male and female donors. In aggregate, our enhanced in vitro MPS model establishes a metabolic baseline and perturbed condition that recapitulates a spectrum of phenotypes observed in MASLD, offering improved quantification and insight into disease progression with relevance to human physiology.
Published in
A microphysiological model of human MASLD reveals paradoxical response to resmetirom
Hellen DJ, Ungerleider J, Tevonian E et al. · Communications biology 2026 · PMID 41535580 · doi:10.1038/s42003-025-09484-9
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 GSE313774_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 PRJNA1381576. Searching any of these in the dataset finder brings you back here.

Study design
33 × NG-A0648

Supports a between-group comparison across 33 samples.

How we read this: 1 replicated groups read from 33 sample titles; they account for 33 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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