GEO series
Acquired genetic and cell state changes in IDH-mutant glioma progression [coculture experiments]
GSE324714
Mus musculus; Homo sapiens
Expression profiling by high throughput sequencing
16 samples
Submitted 2026/04/20
Platform GPL34284Platform GPL35012
Summary
Isocitrate dehydrogenase (IDH)-mutant gliomas are malignant brain tumors that typically arise in early- to mid-adulthood and nearly always recur following treatment. However, the genetic and cellular state changes that drive IDH-mutant glioma progression under treatment remain incompletely understood. Here, we integrated single-nucleus transcriptomic profiles, chromatin accessibility profiles and bulk DNA/RNA sequencing from 75 temporally separated gliomas across 35 patients comprising both the oligodendroglioma and astrocytoma IDH-mutant glioma tumor types. We show that malignant cell states transcriptionally resemble stages of normal glial-neuronal lineage development or a reactive mesenchymal-like state, mirroring states previously described in IDH-wildtype glioblastoma. Malignant cell states displayed distinct chromatin accessibility profiles that were comparable between both IDH-mutant glioma types. The abundance of less differentiated malignant cells increased with grade and with genetic alterations such as PDGFRA amplification. Longitudinal analysis highlighted two major malignant cell state transition patterns. First, reduced lineage differentiation and increased proliferative malignant cells at recurrence were pronounced in gliomas that acquired recurrence-associated genetic events, including treatment-associated hypermutation, increased copy number changes, and cell cycle alterations. Second, increased mesenchymal-like state abundance occurred independently of acquired genetic alterations and instead coincided with heightened macrophage expression. Overall, our findings provide an integrative model that traces the cell-intrinsic and extrinsic factors that shape cellular states during IDH-mutant glioma disease progression.
Published in
Johnson KC, Spitzer A, Varn FS et al.
· Nature 2026
· PMID 42236943
· doi:10.1038/s41586-026-10612-6
This dataset
Download
Direct links to NCBI, no account and no request form: the whole study as GSE324714_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 16 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1436624. Searching any of these in the dataset finder brings you back here.
Study design
4 × MGG152_monoculture vs 4 × MGG152_monoculture_irradiation vs 4 × MGG152_coculture vs 4 × MGG152_coculture_irradiation
Supports a between-group comparison across 16 samples.
4 replicated groups read from 16 sample titles; they account for 16 of them. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9583382 MGG152_monoculture_rep3
- GSM9583383 MGG152_monoculture_irradiation_rep3
- GSM9583384 MGG152_coculture_rep3
- GSM9583385 MGG152_coculture_irradiation_rep3
- GSM9583386 MGG152_monoculture_rep4
- GSM9583387 MGG152_monoculture_irradiation_rep4
- GSM9583388 MGG152_coculture_rep4
- GSM9583389 MGG152_coculture_irradiation_rep4
- GSM9583390 MGG152_monoculture_rep1
- GSM9583391 MGG152_monoculture_irradiation_rep1
- GSM9583392 MGG152_coculture_rep1
- GSM9583393 MGG152_coculture_irradiation_rep1
- GSM9583394 MGG152_monoculture_rep2
- GSM9583395 MGG152_monoculture_irradiation_rep2
- GSM9583396 MGG152_coculture_rep2
- GSM9583397 MGG152_coculture_irradiation_rep2
Similar datasets
- GSE260997 Mutant IDH inhibitors induce lineage differentiation in IDH-mutant Oligodendroglioma III 2458 samples
- GSE270550 Mutant CEBPA promotes tolerance to inflammatory stress through deficient AP-1 activation [RNA-Seq] 75 samples
- GSE296402 Interleukin-23 promotes a pro-inflammatory Th17 cell state by stabilizing RORγt and suppressing glucocorticoid receptor activity 66 samples
- GSE331030 Lentiviral single-cell MPRA of synthetic enhancers reveals motif affinity-based encoding of cell state specificity [sc-lentiMPRA 2] 66 samples
- GSE255972 The oncolytic adenovirus Delta-24-RGD in combination with ONC201 induces a potent antitumor response in pediatric high-grade and diffuse midline glioma models 64 samples
- GSE304029 BRD2 Bromodomain-Mediated Regulation of Cell State Plasticity Modulates Therapy Response in Glioblastoma 56 samples
- GSE241602 Dynamic Chromatin Alteration Induces Oncogenic Hijacking by Nuclear Factor I Family Proteins for Medulloblastoma Progression 30 samples
- GSE248947 Spatiotemporal control of SMARCA5 by a MAPK-RUNX1 axis distinguishes mutant KRAS-driven pancreatic malignancy from tissue regeneration (RNA-Seq) 28 samples
Share this dataset
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.