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Inhibition of Acetyl-CoA metabolic enzymes by EVT0185 impairs hepatic stellate cell activation and reverses MASH and fibrosis in mouse models.

GSE307420 Homo sapiens (human) Single-cell RNA-seq 12 samples Submitted 2025/11/17 Platform GPL11154
At a glance

Single-cell RNA-seq · human · 12 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Samples
12 samples: 3 × LX-2 cells, PRP-empty, TGFb1, DMSO, biol vs 3 × LX-2 cells, PRP-empty, TGFb1, EVT0185, biol vs 3 × LX-2 cells, PRP-SLC27A2, TGFb1, DMSO, biol vs 3 × LX-2 cells, PRP-SLC27A2, TGFb1, EVT0185, biolGroups 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
Dual inhibition of ACLY and ACSS2 by EVT0185 reduces steatosis, hepatic stellate cell activation, and fibrosis in mouse models of MASHCell metabolism · 2026
Summary (written by the submitters)
Metabolic Dysfunction-Associated Steatohepatitis (MASH) is characterized by liver steatosis and inflammation which lead to fibrosis following hepatic stellate cell (HSC) activation. Acetyl-CoA is fundamental for de novo lipogenesis (DNL) and cholesterol synthesis and can be derived from citrate via ATP citrate lyase (ACLY), or from acetate via acetyl-CoA synthetase (ACSS2).
Read the full summary ↓
Here, we find that EVT0185, an ACLY and ACSS2 inhibitor, leads to resolution of MASH and fibrosis while lowering insulin and glucose in four distinct mouse models. EVT0185 also reduces fibrosis alone and in combination with semaglutide and more effectively than bempedoic acid in a model not characterized by steatosis or insulin resistance. Spatial transcriptomic and scRNAseq reveal marked downregulation of cholesterol synthesis in HSCs with EVT0185 treatment in vivo and in vitro. These data indicate a critical role for ACLY and ACSS2 in HSCs and suggest further clinical evaluation of EVT0185 for reducing MASH and fibrosis may be warranted.
Published in
Dual inhibition of ACLY and ACSS2 by EVT0185 reduces steatosis, hepatic stellate cell activation, and fibrosis in mouse models of MASH
Di Pastena F, Gautam J, Lally JSV et al. · Cell metabolism 2026 · PMID 41500198 · doi:10.1016/j.cmet.2025.11.015
This dataset
Open GSE307420 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 GSE307420_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 PRJNA1321593 and SRA study SRP618238. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41500198) ↗
Study design
3 × LX-2 cells, PRP-empty, TGFb1, DMSO, biol vs 3 × LX-2 cells, PRP-empty, TGFb1, EVT0185, biol vs 3 × LX-2 cells, PRP-SLC27A2, TGFb1, DMSO, biol vs 3 × LX-2 cells, PRP-SLC27A2, TGFb1, EVT0185, biol

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
Datasets on a similar topic

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