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ARID1A and ARID1B preserve B cell identity, prevent myeloid transformation and reveal therapeutic vulnerabilities

GSE307527 Homo sapiens (human) RNA-seq (gene expression) 30 samples Submitted 2025/09/15 Platform GPL24676Platform GPL24247
At a glance

RNA-seq (gene expression) · human · 30 samples

What it is
RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism
Homo sapiens (human)
Samples
30 samples: 6 conditions, mostly with about 6 replicates eachGroups 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
ARID1A and ARID1B preserve B cell identity, prevent myeloid transformation and reveal therapeutic vulnerabilitiesbioRxiv : the preprint server for biology · 2025
Summary (written by the submitters)
Chromatin remodeling by the SWI/SNF complex is essential for hematopoietic lineage commitment and differentiation. While core subunits ARID1A and ARID1B are frequently mutated in B cell malignancies, their specific roles in B cell development and transformation remain poorly understood. Here, we investigated the function of these SWI/SNF components using conditional knockout mice with CD19-Cre–mediated deletion, initiated at the pro-B cell stage.
Read the full summary ↓
Loss of either Arid1a or Arid1b led to a partial block in B cell differentiation in the bone marrow and impaired germinal center formation following antigen exposure. Double deletion of Arid1a and Arid1b resulted in a more severe phenotype, with marked reduction in peripheral B cells, shortened overall survival, and development of an aggressive leukemia. Surprisingly, the malignancy was of myeloid origin, arising from a small subset of CD19-expressing multipotent progenitors (MPPs). These Arid1a/Arid1b-deficient MPPs exhibited abnormal expansion, defective differentiation in methylcellulose assays, and transcriptional dysregulation of key self-renewal programs driven by CBFA2T3 (ETO2) and Fli1. In established B cell lymphoma cells in vitro, loss of ARID1A and ARID1B together mildly affected cell growth, while loss of ARID1A increased sensitivity to pharmacological EZH2 inhibition. Collectively, our findings reveal stage-specific and compensatory roles for ARID1A and ARID1B in B cell development, uncover a previously unrecognized mechanism by which SWI/SNF loss in early progenitors can drive transformation towards myeloid leukemia, and identified possible therapeutic vulnerabilities in patients with ARID1A mutations.
Published in
ARID1A and ARID1B preserve B cell identity, prevent myeloid transformation and reveal therapeutic vulnerabilities
Lin PN, Park J, Kang YA et al. · bioRxiv : the preprint server for biology 2025 · PMID 41000613 · doi:10.1101/2025.09.16.676393
This dataset
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.

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 GSE307527_RAW.tar (it can run to tens of gigabytes).

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.

What the files usually look like: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1321923 and SRA study SRP618480. Searching any of these in the dataset finder brings you back here.

Study design
6 conditions, mostly with about 6 replicates each
SUDHL6-ARID1A-KO, ×6 SUDHL6-ARID1B-KO, ×6 SUDHL6-NTCTRL, ×6 mouse_MPP2-3-Ctrl, ×6 SUDHL6-ARID1A-ARID1B-double KO, ×3 mouse_MPP2-3-Arid1a-Arid1b dKO, ×3

Supports a between-group comparison across 30 samples.

How we read this: 6 replicated groups read from 30 sample titles; they account for 30 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
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