GEO series

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

GSE269188 Mus musculus (mouse) Single-cell RNA-seq 331 samples Submitted 2025/03/10 Platform GPL24247

At a glance

Single-cell RNA-seq · mouse · 331 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: 331 samples: 331 × 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 GSE269188 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 GSE269188_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 PRJNA1120479 and SRA study SRP512050. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40215981) ↗

Study design

331 × BMDMs, AB

Supports a between-group comparison across 331 samples.

How we read this: 1 replicated groups read from 331 sample titles; they account for 331 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

GSM8307796 BMDMs, AB9052 BMDMs, AB
GSM8307797 BMDMs, AB9053 BMDMs, AB
GSM8307798 BMDMs, AB9054 BMDMs, AB
GSM8307799 BMDMs, AB9055 BMDMs, AB
GSM8307800 BMDMs, AB9056 BMDMs, AB
GSM8307801 BMDMs, AB9057 BMDMs, AB
GSM8307802 BMDMs, AB9058 BMDMs, AB
GSM8307803 BMDMs, AB9059 BMDMs, AB
GSM8307804 BMDMs, AB9061 BMDMs, AB
GSM8307805 BMDMs, AB9062 BMDMs, AB
GSM8307806 BMDMs, AB9063 BMDMs, AB
GSM8307807 BMDMs, AB9064 BMDMs, AB
GSM8307808 BMDMs, AB9065 BMDMs, AB
GSM8307809 BMDMs, AB9066 BMDMs, AB
GSM8307810 BMDMs, AB9067 BMDMs, AB
GSM8307811 BMDMs, AB9068 BMDMs, AB
GSM8307812 BMDMs, AB9069 BMDMs, AB
GSM8307813 BMDMs, AB9070 BMDMs, AB
GSM8307814 BMDMs, AB9071 BMDMs, AB
GSM8307815 BMDMs, AB9072 BMDMs, AB
GSM8307816 BMDMs, AB9073 BMDMs, AB
GSM8307817 BMDMs, AB9074 BMDMs, AB
GSM8307818 BMDMs, AB9075 BMDMs, AB
GSM8307819 BMDMs, AB9076 BMDMs, AB
GSM8307820 BMDMs, AB9077 BMDMs, AB
GSM8307821 BMDMs, AB9078 BMDMs, AB
GSM8307822 BMDMs, AB9079 BMDMs, AB
GSM8307823 BMDMs, AB9080 BMDMs, AB
GSM8307824 BMDMs, AB9081 BMDMs, AB
GSM8307825 BMDMs, AB9082 BMDMs, AB
GSM8307826 BMDMs, AB9083 BMDMs, AB
GSM8307827 BMDMs, AB9084 BMDMs, AB
GSM8307828 BMDMs, AB9085 BMDMs, AB
GSM8307829 BMDMs, AB9086 BMDMs, AB
GSM8307830 BMDMs, AB9087 BMDMs, AB
GSM8307831 BMDMs, AB9088 BMDMs, AB
GSM8307832 BMDMs, AB9089 BMDMs, AB
GSM8307833 BMDMs, AB9090 BMDMs, AB
GSM8307834 BMDMs, AB9091 BMDMs, AB
GSM8307835 BMDMs, AB9092 BMDMs, AB

+ 291 more — browse all 331 samples with per-sample file links →

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GSE269187 ZEB2 is a Master Switch Controlling the Tumor-Associated Macrophage Program [in vitro] 17 samples shares zeb2, tumor-associated, controlling, macrophage, program, master, switch
GSE324935 IFN-γ and TLR9 signaling reprogram tumor-associated macrophages to promote antitumor immunity in melanoma 20 samples shares tumor-associated, macrophage, program
GSE300757 Efferocytosis induces proangiogenic function and chromatin remodeling in tumor-associated macrophages 127 samples shares tumor-associated, macrophage
GSE280003 Gpnmb and Spp1 mark a conserved macrophage injury response masking fibrosis-specific programming in the lung 81 samples shares macrophage, program
GSE276628 Reciprocal genetic screens identify epigenetics factors controlling epidermal cell activation. [RNAseq_MiniBulk] 41 samples shares controlling, screen
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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

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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.