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Precision targeting of beta-catenin induces tumor reprogramming and immunity in hepatocellular cancers [Bulk RNA-seq CTNNB1/hMet/NFE2L2]

GSE270414 Mus musculus (mouse) Single-cell RNA-seq 13 samples Submitted 2025/05/02 Platform GPL21626
At a glance

Single-cell RNA-seq · mouse · 13 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
Mus musculus (mouse)
Samples
13 samples: 4 × Met_Bcat_TREAT_BL vs 3 × Met_Bcat_CTRL_BL vs 3 × Nrf2_Bcat_CTRL_BL vs 3 × Nrf2_Bcat_TREAT_BLGroups 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
Precision targeting of β-catenin induces tumor reprogramming and immunity in hepatocellular cancersNature communications · 2025
Summary (written by the submitters)
First-line immune checkpoint inhibitor (ICI) combinations have shown responses in subsets of patients with advanced hepatocellular carcinoma (HCC). Nearly half of patients are Wnt active with mutations in CTNNB1 (encoding for beta-catenin), AXIN1/2, or APC, and demonstrate limited benefit to ICI due to an immunosuppressive tumor microenvironment.
Read the full summary ↓
We investigated a novel siRNA encapsulated in lipid nanoparticle targeting CTNNB1 (LNP-CTNNB1) in multiple beta-catenin-mutated immunocompetent HCC mouse models, observing complete response. Integrated single-cell and spatial transcriptomics revealed complete cellular and zonal reprogramming of CTNNB1-mutated tumors, and a spatiotemporal shift in innate immune surveillance with intra-tumoral pro-inflammatory myeloid infiltration following LNP-CTNNB1 intervention. beta-catenin knockdown initiated tumor cell-intrinsic type I/II interferon signaling accompanied by IRF2 upregulation, which was suppressed in CTNNB1-mutated HCCs. IRF2 re-expression in beta-catenin-mutated HCC restored adaptive tumor immunity with increased CD4+ T cells and impaired recruitment of resident T regulatory cells. Finally, LNP-CTNNB1 synergized with ICI in advanced-stage disease through increasing intra-tumoral recruitment of cytotoxic T cells. In summary, RNAi-mediated inhibition of CTNNB1 is efficacious as monotherapy and in combination with ICI in CTNNB1-mutated HCCs through remodeling both tumor cell intrinsic signaling and global immune surveillance, thus providing rationale for clinical investigations.
Published in
Precision targeting of β-catenin induces tumor reprogramming and immunity in hepatocellular cancers
Lehrich BM, Delgado ER, Yasaka TM et al. · Nature communications 2025 · PMID 40442146 · doi:10.1038/s41467-025-60457-2
This dataset
Open GSE270414 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 GSE270414_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 PRJNA1126389 and SRA study SRP515159. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40442146) ↗
Study design
4 × Met_Bcat_TREAT_BL vs 3 × Met_Bcat_CTRL_BL vs 3 × Nrf2_Bcat_CTRL_BL vs 3 × Nrf2_Bcat_TREAT_BL

Supports a between-group comparison across 13 samples.

How we read this: 4 replicated groups read from 13 sample titles; they account for 13 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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