GEO series
ARID1A and ARID1B preserve B cell identity, prevent myeloid transformation and reveal therapeutic vulnerabilities
GSE307527
Homo sapiens; Mus musculus
Expression profiling by high throughput sequencing
30 samples
Submitted 2025/09/15
Platform GPL24676Platform GPL24247
Summary
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. 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
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
Direct links to NCBI, no account and no request form: the whole study as GSE307527_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 30 samples. Raw sequencing reads are also available from ENA.
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.
6 replicated groups read from 30 sample titles; they account for 30 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9226038 SUDHL6-ARID1A-KO, bio rep 1
- GSM9226039 SUDHL6-ARID1A-KO, bio rep 2
- GSM9226040 SUDHL6-ARID1A-KO, bio rep 3
- GSM9226041 SUDHL6-ARID1A-KO, bio rep 4
- GSM9226042 SUDHL6-ARID1A-KO, bio rep 5
- GSM9226043 SUDHL6-ARID1A-KO, bio rep 6
- GSM9226044 SUDHL6-ARID1B-KO, bio rep 1
- GSM9226045 SUDHL6-ARID1B-KO, bio rep 2
- GSM9226046 SUDHL6-ARID1B-KO, bio rep 3
- GSM9226047 SUDHL6-ARID1B-KO, bio rep 4
- GSM9226048 SUDHL6-ARID1B-KO, bio rep 5
- GSM9226049 SUDHL6-ARID1B-KO, bio rep 6
- GSM9226050 SUDHL6-ARID1A-ARID1B-double KO, bio rep 1
- GSM9226051 SUDHL6-ARID1A-ARID1B-double KO, bio rep 2
- GSM9226052 SUDHL6-ARID1A-ARID1B-double KO, bio rep 3
- GSM9226053 SUDHL6-NTCTRL, bio rep 1
- GSM9226054 SUDHL6-NTCTRL, bio rep 2
- GSM9226055 SUDHL6-NTCTRL, bio rep 3
- GSM9226056 SUDHL6-NTCTRL, bio rep 4
- GSM9226057 SUDHL6-NTCTRL, bio rep 5
- GSM9226058 SUDHL6-NTCTRL, bio rep 6
- GSM9226059 mouse_MPP2-3-Ctrl, bio rep 1
- GSM9226060 mouse_MPP2-3-Ctrl, bio rep 2
- GSM9226061 mouse_MPP2-3-Ctrl, bio rep 3
- GSM9226062 mouse_MPP2-3-Ctrl, bio rep 4
- GSM9226063 mouse_MPP2-3-Ctrl, bio rep 5
- GSM9226064 mouse_MPP2-3-Ctrl, bio rep 6
- GSM9226065 mouse_MPP2-3-Arid1a-Arid1b dKO, bio rep 1
- GSM9226066 mouse_MPP2-3-Arid1a-Arid1b dKO, bio rep 2
- GSM9226067 mouse_MPP2-3-Arid1a-Arid1b dKO, bio rep 3
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