GEO series

Multiomic analysis uncovers a continuous spectrum of differentiation and Wnt-MDK-driven immune evasion in hepatoblastoma [Spatial Transcriptomics]

GSE261958 Homo sapiens (human) Spatial transcriptomics 22 samples Submitted 2025/02/07 Platform GPL30173

At a glance

Spatial transcriptomics · human · 22 samples

What it is: Spatial transcriptomicsGene activity measured with its position in a tissue section.
Organism: Homo sapiens (human)
Samples: 22 samples: 22 × Hepatoblastoma sampleGroups 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: Multiomic analysis uncovers a continuous spectrum of differentiation and Wnt-MDK-driven immune evasion in hepatoblastomaJournal of hepatology · 2025

Summary (written by the submitters)

Background & Aims: Hepatoblastoma is the most common pediatric cancer of the liver and the majority of cases display activating mutations in the Wnt/β-catenin pathway. Understanding the complex milieu of the tumor microenvironment has resulted in promising new therapies for adult cancers, but similar approaches in pediatric cancers are still lacking.

Read the full summary ↓

We aimed to provide a comprehensive analysis of the tumor microenvironment of hepatoblastoma unveiling its spatial architecture and key signaling mechanisms. Methods: Single-cell/-nucleus RNA-seq (n=15), spatial transcriptomics (n=22), and multiplex immunofluorescence stainings (n=7) of treated, untreated, and metastasized pediatric hepatoblastomas were performed. An RNA-seq validation cohort (n=110) including hepatoblastoma, non-tumor and fetal liver samples and single-cell RNA-seq data of healthy immune cells were used for further analysis. Western blotting and RNA-seq of hepatoblastoma and macrophage cell lines were conducted for experimental validation. Results: Of four identified transcriptional tumor programs, “Developmental” and “Metabolic” reflected different hepatic differentiation stages, while “Cycling” was enriched in undifferentiated cells and relapsed samples, and “Intermediate” displayed high activity in samples from patients with poor outcomes. We discovered an increased ratio of anti- to pro-inflammatory immune cells and evidence of immune exclusion from tumor areas. Wnt-responsive upregulation of the immunomodulator midkine in hepatoblastoma cells was associated with a change in macrophage phenotype, which could be partially reversed through midkine inhibition. Conclusions: Hepatoblastoma cells exist along a continuous spectrum of hepatic differentiation and inhabit an altered immune environment. Wnt signaling augments midkine expression, which appears to be involved in shaping the immune environment by modifying macrophages to enable immune evasion, thereby providing a potential therapeutic target.

Published in

Multiomic analysis uncovers a continuous spectrum of differentiation and Wnt-MDK-driven immune evasion in hepatoblastoma

Münter D, de Faria FW, Richter M et al. · Journal of hepatology 2025 · PMID 39900120 · doi:10.1016/j.jhep.2025.01.031

This dataset

Open GSE261958 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 GSE261958_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: Spatial studies usually ship Space Ranger style folders (count matrix plus tissue images). Look for them among the supplementary files.

Also filed as BioProject PRJNA1089624 and SRA study SRP496478. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39900120) ↗

Study design

22 × Hepatoblastoma sample

Supports a between-group comparison across 22 samples.

How we read this: 1 replicated groups read from 22 sample titles; they account for 22 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

GSM8155169 Hepatoblastoma sample 11 Hepatoblastoma sample
GSM8155170 Hepatoblastoma sample 12 Hepatoblastoma sample
GSM8155171 Hepatoblastoma sample 13 Hepatoblastoma sample
GSM8155172 Hepatoblastoma sample 14 Hepatoblastoma sample
GSM8155173 Hepatoblastoma sample 15 Hepatoblastoma sample
GSM8155174 Hepatoblastoma sample 16 Hepatoblastoma sample
GSM8155175 Hepatoblastoma sample 17 Hepatoblastoma sample
GSM8155176 Hepatoblastoma sample 18 Hepatoblastoma sample
GSM8155177 Hepatoblastoma sample 19 Hepatoblastoma sample
GSM8155178 Hepatoblastoma sample 20 Hepatoblastoma sample
GSM8657777 Hepatoblastoma sample 21 Hepatoblastoma sample
GSM8657778 Hepatoblastoma sample 22 Hepatoblastoma sample
GSM8657779 Hepatoblastoma sample 23 Hepatoblastoma sample
GSM8657780 Hepatoblastoma sample 24 Hepatoblastoma sample
GSM8657781 Hepatoblastoma sample 25 Hepatoblastoma sample
GSM8657782 Hepatoblastoma sample 26 Hepatoblastoma sample
GSM8657783 Hepatoblastoma sample 27 Hepatoblastoma sample
GSM8657784 Hepatoblastoma sample 28 Hepatoblastoma sample
GSM8657785 Hepatoblastoma sample 29 Hepatoblastoma sample
GSM8657786 Hepatoblastoma sample 30 Hepatoblastoma sample
GSM8657787 Hepatoblastoma sample 31 Hepatoblastoma sample
GSM8657788 Hepatoblastoma sample 32 Hepatoblastoma sample

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