GEO series
BRD2 Bromodomain-Mediated Regulation of Cell State Plasticity Modulates Therapy Response in Glioblastoma
GSE304029
Mus musculus; Homo sapiens
Expression profiling by high throughput sequencing
56 samples
Submitted 2025/11/17
Platform GPL24676Platform GPL34284Platform GPL34290
Summary
Background: Glioblastoma (GBM) displays remarkable cell state plasticity, a major contributor to therapeutic resistance and tumor progression. While epigenetic mechanisms play a central role in driving this plasticity, the key regulators remain poorly understood, and developing effective therapeutic strategies targeting them has been challenging. Methods: We investigated the role of BRD2, a key regulator of NF-κB mediated mesenchymal (MES) transition, using GBM patient-derived xenograft (PDX) cell lines, CRISPR-mediated knock-in/knockout approaches, RNA-seq, and in vitro and in vivo modeling. BET inhibitors were employed to target MES gene expression and sensitize GBM to radiation therapy. Results: We found that PTEN loss induces RelA chromatin localization and acetylation-mediated recruitment of BRD2 to the MES gene promoters. BRD2 binding is essential for maintaining MES gene expression and phenotype. Genetic ablation or loss-of-function mutation of BRD2 bromodomains reverses MES transition, enhances radiation sensitivity, and improves survival in orthotopic xenograft models. Additionally, treatment with a brain-penetrant BD2-selective inhibitor suppresses the MES phenotype and increases radiation sensitivity of GBM stem cells in vitro. Conclusion: Our study identifies BRD2 as a key mediator of MES transition in GBM, with its bromodomains playing a crucial role in driving cell state plasticity. Targeting BRD2 with BD2-selective inhibitors offers a promising therapeutic strategy to overcome radiation resistance and improve outcomes for GBM patients.
Published in
Vadla R, Taylor B, Miyake Y et al.
· Neuro-oncology 2025
· PMID 40686478
· doi:10.1093/neuonc/noaf169
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE304029_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 56 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1298802 and SRA study SRP604626. Searching any of these in the dataset finder brings you back here.
Study design
14 conditions, mostly in triplicate
GSC11 cells, shControl ×3
GSC11 cells, shBRD2 ×3
GSC11 cells, RelA K310 ×3
GSC11 cells, BRD2_WT ×3
GSC11 cells, BRD2_BD1 ×3
GSC11 cells, BRD2_BD2 ×3
GSC11 cells, BRD2_BD1/2 ×3
TS576 cell, PTENKO ×3
+6 more
Supports a between-group comparison across 40 samples.
14 replicated groups read from the first 40 of 56 sample titles; they account for 40 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9141164 GSC11 cells, shControl_1
- GSM9141165 GSC11 cells, shControl_2
- GSM9141166 GSC11 cells, shControl_3
- GSM9141167 GSC11 cells, shBRD2_1
- GSM9141168 GSC11 cells, shBRD2_2
- GSM9141169 GSC11 cells, shBRD2_3
- GSM9141170 GSC11 cells, RelA K310R_1
- GSM9141171 GSC11 cells, RelA K310R_2
- GSM9141172 GSC11 cells, RelA K310R_3
- GSM9141173 GSC11 cells, BRD2_WT_1
- GSM9141174 GSC11 cells, BRD2_WT_2
- GSM9141175 GSC11 cells, BRD2_WT_3
- GSM9141176 GSC11 cells, BRD2_BD1_1
- GSM9141177 GSC11 cells, BRD2_BD1_2
- GSM9141178 GSC11 cells, BRD2_BD1_3
- GSM9141179 GSC11 cells, BRD2_BD2_1
- GSM9141180 GSC11 cells, BRD2_BD2_2
- GSM9141181 GSC11 cells, BRD2_BD2_3
- GSM9141182 GSC11 cells, BRD2_BD1/2_1
- GSM9141183 GSC11 cells, BRD2_BD1/2_2
- GSM9141184 GSC11 cells, BRD2_BD1/2_3
- GSM9141185 TS576 cell, parental_1
- GSM9141186 TS576 cell, parental_2
- GSM9141187 TS576 cell, PTENKO_1
- GSM9141188 TS576 cell, PTENKO_2
- GSM9141189 TS576 cell, PTENKO_3
- GSM9141190 GSC11 cells, DMSO_1
- GSM9141191 GSC11 cells, DMSO_2
- GSM9141192 GSC11 cells, DMSO_3
- GSM9141193 GSC11 cells, GSK620_1
- GSM9141194 GSC11 cells, GSK620_2
- GSM9141195 GSC11 cells, GSK620_3
- GSM9141196 GSC23 cells, DMSO_1
- GSM9141197 GSC23 cells, DMSO_2
- GSM9141198 GSC23 cells, DMSO_3
- GSM9141199 GSC23 cells, GSK620_1
- GSM9141200 GSC23 cells, GSK620_2
- GSM9141201 GSC23 cells, GSK620_3
- GSM9141202 GSC23 cells, BRD2_WT_1
- GSM9141203 GSC23 cells, BRD2_WT_2
+ 16 more — browse all 56 samples with per-sample file links →
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