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BACH2 dosage establishes the hierarchy of stemness and fine-tunes antitumor immunity in CAR T cells

GSE283635 Mus musculus (mouse) ChIP-seq / ATAC-seq (genome binding and open chromatin) 18 samples Submitted 2025/10/06 Platform GPL24247Platform GPL21626
At a glance

ChIP-seq / ATAC-seq (genome binding and open chromatin) · mouse · 18 samples

What it is
ChIP-seq / ATAC-seq (genome binding and open chromatin)Where proteins bind the genome, or which regions are open and active.
Organism
Mus musculus (mouse)
Samples
18 samples: 5 conditions, mostly in duplicateGroups 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
BACH2 dosage establishes the hierarchy of stemness and fine-tunes antitumor immunity in CAR T cellsNature immunology · 2026
Summary (written by the submitters)
Self-renewing stem-like T cells promote the efficacy of cancer immunotherapy and are a heterogeneous population with sub-lineages demonstrating different degrees of stemness. At the apex of this hierarchy is long-term (LT) stem-like T cells with the highest capacity of persistence, repopulation and response to immune checkpoint inhibitors (ICI).
Read the full summary ↓
However, the pathway that establishes the hierarchy of stemness in chimeric antigen receptor (CAR) T cells and its role in antitumor efficacy of CAR T cells are unclear. Here, we demonstrate that LT stem-like differentiation and antitumor immunity of CAR T cells are dose-dependently regulated by BACH2. Pre-infusion LT stem-like CAR T cells showed epigenetic activation of BACH2 and superior antitumor response in mice and humans. After clearing tumor in vivo, LT stem-like T cells emerged as a CAR subset that transcriptionally and epigenetically upregulated BACH2 and downregulated TOX. Loss-of-function experiments revealed an essential role of BACH2 in the antitumor response of CAR T cells and the transcriptional program of LT stem-like CAR T cells. In exhaustion-prone GD2 CAR T cells with high tonic signaling, we showed that quantitative control of BACH2 protein level by a small molecule drug fine-tuned the degree of stemness and exhaustion in CAR T cells. Chemically inducing temporal BACH2 activation during manufacture of GD2 CAR T cells imprinted greater antitumor immunity against solid tumor after infusion. Together, we show that BACH2 dosage establishes the hierarchy of stem-like CAR T cells and can be temporally and tunably controlled in CAR T cells to optimize differentiation and antitumor immunity.
Published in
BACH2 dosage establishes the hierarchy of stemness and fine-tunes antitumor immunity in CAR T cells
Hu T, Zhu Z, Luo Y et al. · Nature immunology 2026 · PMID 41545542 · doi:10.1038/s41590-025-02388-0
This dataset
Open GSE283635 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 GSE283635_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: Look for peak files (.bed, .narrowPeak) and signal tracks (.bigWig) among the supplementary files; the raw reads are on ENA.

Also filed as BioProject PRJNA1194953 and SRA study SRP549739. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41545542) ↗
Study design
5 conditions, mostly in duplicate
ChIPseq_CD19_CAR_T_Control_IgG_IP ×2 ChIPseq_CD19_CAR_T_BACH2OE_IgG_IP ×2 ChIPseq_CD19_CAR_T_BACH2OE_BACH2_IP ×2 ChIPseq_CD19_CAR_T_Control_JUNB_IP ×2 ChIPseq_CD19_CAR_T_BACH2OE_JUNB_IP ×2 scRNAseq_Multiome_CAR_T_in_vitro ×1 scATACseq_Multiome_CAR_T_in_vitro ×1 scRNAseq_Multiome_E2APBX1_CAR_T_D20_Spleen ×1 +5 more

Supports a between-group comparison across 10 samples.

How we read this: 5 replicated groups read from 18 sample titles; they account for 10 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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