GEO series

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

GSE269187 Mus musculus (mouse) Single-cell RNA-seq 17 samples Submitted 2025/03/10 Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 17 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: 17 samples: 17 × BMDMs, 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 GSE269187 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 GSE269187_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 PRJNA1120478 and SRA study SRP512056. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40215981) ↗

Study design

17 × BMDMs, AB

Supports a between-group comparison across 17 samples.

How we read this: 1 replicated groups read from 17 sample titles; they account for 17 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

GSM8307779 BMDMs, AB12212 BMDMs, AB
GSM8307780 BMDMs, AB12213 BMDMs, AB
GSM8307781 BMDMs, AB12214 BMDMs, AB
GSM8307782 BMDMs, AB12215 BMDMs, AB
GSM8307783 BMDMs, AB12216 BMDMs, AB
GSM8307784 BMDMs, AB12217 BMDMs, AB
GSM8307785 BMDMs, AB12219 BMDMs, AB
GSM8307786 BMDMs, AB12220 BMDMs, AB
GSM8307787 BMDMs, AB12221 BMDMs, AB
GSM8307788 BMDMs, AB12222 BMDMs, AB
GSM8307789 BMDMs, AB12223 BMDMs, AB
GSM8307790 BMDMs, AB12224 BMDMs, AB
GSM8307791 BMDMs, AB12225 BMDMs, AB
GSM8307792 BMDMs, AB12226 BMDMs, AB
GSM8307793 BMDMs, AB12233 BMDMs, AB
GSM8307794 BMDMs, AB12234 BMDMs, AB
GSM8307795 BMDMs, AB12235 BMDMs, AB

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GSE300757 Efferocytosis induces proangiogenic function and chromatin remodeling in tumor-associated macrophages 127 samples shares tumor-associated, macrophage
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GSE237783 Complex interaction of tumor-derived factors instructs the niche specific phenotypes of tumor-associated macrophages [RNA-Seq] 28 samples shares tumor-associated, macrophage
GSE335147 Mitochondrial profiling across macrophage states reveals inhibition of IL-4/IL-13 reprogramming by the integrated stress response 24 samples shares macrophage, program
GSE99296 α-ketoglutarate orchestrates macrophage activation through metabolic and epigenetic reprogramming 18 samples shares macrophage, program

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