GEO series

ZEB2 is a Master Switch Controlling the Tumor-Associated Macrophage Program [in vivo]

GSE269191 Mus musculus (mouse) Single-cell RNA-seq 145 samples Submitted 2025/03/10 Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 145 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: 145 samples: 145 × CD45 cells, ABGroups 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: ZEB2 is a master switch controlling the tumor-associated macrophage programCancer cell · 2025

Summary (written by the submitters)

Tumor-associated macrophages (TAMs) are major players in regulating the immunosuppressive tumor environment, and their abundance is highly correlated with poor clinical outcomes. Here, we constructed a TAM regulatory network by integrating scRNA-seq data across human solid tumors with a dedicated CRISPR knockout screen. Using a deep generative model capable of learning a local representation for each candidate regulator, we constructed a gene perturbation network that linked individual target genes with prototypical functional modules in TAMs.

Read the full summary ↓

We identified non-redundant pathways regulating distinct TAM functions, showing modular circuitry. For instance, the complement module is repressed by Stat6, Zeb2, Gpnmb, and Spp1, while the Tgfbr1-Smad2/4 pathway induces this program in TAMs. Importantly, we identified Zeb2 as the master regulator of pro-tumor functions in TAMs, orchestrating the suppression of type I interferon response and antigen presentation alongside the activation of immune suppression programs. Genetic ablation of Zeb2 reprogrammed TAMs identity on chromatin, RNA, and protein levels. In human tumors with high macrophage content, ZEB2 expression was associated with poor prognosis in solid cancers, including lung and bladder. Functional macrophage coculturing assays defined Zeb2 as a critical regulator of TAM immunosuppression activity by inhibiting T cell proliferation and activation. Selective in vivo targeting of Zeb2 in macrophages using a CpGsiRNAZeb2 DNA hybrid reprogrammed TAMs and mobilized systematic anti-tumoral T cell responses, achieving complete tumor clearance as a monotherapy. Overall, our study generated a detailed genetic roadmap of TAM gene circuits and identified ZEB2 as a master switch of TAMs with potential therapeutic implications for macrophage-based immunotherapies.

Published in

ZEB2 is a master switch controlling the tumor-associated macrophage program

Sheban F, Phan TS, Xie K et al. · Cancer cell 2025 · PMID 40215981 · doi:10.1016/j.ccell.2025.03.021

This dataset

Open GSE269191 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 GSE269191_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 PRJNA1120486 and SRA study SRP512051. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40215981) ↗

Study design

145 × CD45 cells, AB

Supports a between-group comparison across 145 samples.

How we read this: 1 replicated groups read from 145 sample titles; they account for 145 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

GSM8308139 CD45 cells, AB12741 CD45 cells, AB
GSM8308140 CD45 cells, AB12742 CD45 cells, AB
GSM8308141 CD45 cells, AB12743 CD45 cells, AB
GSM8308142 CD45 cells, AB12744 CD45 cells, AB
GSM8308143 CD45 cells, AB12745 CD45 cells, AB
GSM8308144 CD45 cells, AB12746 CD45 cells, AB
GSM8308145 CD45 cells, AB12747 CD45 cells, AB
GSM8308146 CD45 cells, AB12748 CD45 cells, AB
GSM8308147 CD45 cells, AB12749 CD45 cells, AB
GSM8308148 CD45 cells, AB12750 CD45 cells, AB
GSM8308149 CD45 cells, AB12751 CD45 cells, AB
GSM8308150 CD45 cells, AB12752 CD45 cells, AB
GSM8308151 CD45 cells, AB12753 CD45 cells, AB
GSM8308152 CD45 cells, AB12754 CD45 cells, AB
GSM8308153 CD45 cells, AB12755 CD45 cells, AB
GSM8308154 CD45 cells, AB12756 CD45 cells, AB
GSM8308155 CD45 cells, AB12759 CD45 cells, AB
GSM8308156 CD45 cells, AB12760 CD45 cells, AB
GSM8308157 CD45 cells, AB12761 CD45 cells, AB
GSM8308158 CD45 cells, AB12762 CD45 cells, AB
GSM8308159 CD45 cells, AB12763 CD45 cells, AB
GSM8308160 CD45 cells, AB12764 CD45 cells, AB
GSM8308161 CD45 cells, AB12765 CD45 cells, AB
GSM8308162 CD45 cells, AB12766 CD45 cells, AB
GSM8308163 CD45 cells, AB12767 CD45 cells, AB
GSM8308164 CD45 cells, AB12768 CD45 cells, AB
GSM8308165 CD45 cells, AB12769 CD45 cells, AB
GSM8308166 CD45 cells, AB12770 CD45 cells, AB
GSM8308167 CD45 cells, AB12771 CD45 cells, AB
GSM8308168 CD45 cells, AB12772 CD45 cells, AB
GSM8308169 CD45 cells, AB12773 CD45 cells, AB
GSM8308170 CD45 cells, AB12774 CD45 cells, AB
GSM8308171 CD45 cells, AB12775 CD45 cells, AB
GSM8308172 CD45 cells, AB12776 CD45 cells, AB
GSM8308173 CD45 cells, AB12777 CD45 cells, AB
GSM8308174 CD45 cells, AB12778 CD45 cells, AB
GSM8308175 CD45 cells, AB12779 CD45 cells, AB
GSM8308176 CD45 cells, AB12780 CD45 cells, AB
GSM8308177 CD45 cells, AB12887 CD45 cells, AB
GSM8308178 CD45 cells, AB12888 CD45 cells, AB

+ 105 more — browse all 145 samples with per-sample file links →

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Search all mouse RNA-seq datasets in GEO →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.