GEO series
Dissecting cellular state alterations critical for the synergistic response and therapy resistance of the combined Abemaciclib, Temozolomide, and Radiation in DIPG PDOX models
GSE301111
Homo sapiens; Mus musculus
Expression profiling by high throughput sequencing
14 samples
Submitted 2026/08/07
Platform GPL34284Platform GPL34290
Summary
Diffuse intrinsic pontine glioma (DIPG) is a lethal pediatric brain cancer. Here, we demonstrated that combining the CDK4/6 inhibitor abemaciclib with temozolomide and radiation (the triple therapy) yields synergistic anti-tumor effects in DIPG organoids and significantly extends survival times in patient-derived orthotopic (intra-brain stem) xenograft (PDOX) models. Mechanistically, we performed scRNA-seq and identified dynamic reprogramming of tumor cell states, including the expansion of NPC-like, depletion of OPC- and AC-like subpopulations, and persistence of MES-like and mitotic-like cells, that contributed to therapeutic resistance. Pseudotime trajectory analysis further revealed therapy-induced cell fate transitions within NPC- and OPC-like compartments, including the enrichment of stem-like cells. More importantly, we discovered that an alternative trajectory—exit from stemness toward more differentiated states—may also contribute to therapeutic failure. Additionally, we identified a novel radiation-resistant subpopulation and found a new set of transcriptional targets indicative of therapeutic vulnerability. This study demonstrated the triple therapy as a promising DIPG regimen that can be rapidly translated into clinical trials and nominated new cellular and molecular targets to overcome residual disease.
Published in
Huang ZL, Jiang T, Suarez Palacios MM et al.
· Cancer letters 2026
· PMID 42532370
· doi:10.1016/j.canlet.2026.218771
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE301111_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 14 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1283950 and SRA study SRP597919. Searching any of these in the dataset finder brings you back here.
Study design
13 conditions, each sampled once — no replicated groups
IBs-A0317DIPG PDOX model treated with temozol… ×2
Supports a case/control comparison: 11 samples read as cases, 2 as controls.
Read from 14 sample titles: 13 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM9075542 IBs-A0317DIPG PDOX model under control group
- GSM9075543 IBs-A0317DIPG PDOX model treated with abemaciclib
- GSM9075544 IBs-A0317DIPG PDOX model treated with radiation
- GSM9075545 IBs-A0317DIPG PDOX model treated with temozolomide and radiation_biol rep 1
- GSM9075546 IBs-A0317DIPG PDOX model treated with temozolomide and radiation_biol rep 2
- GSM9075547 IBs-A0317DIPG PDOX model treated with abemaciclib and radiation
- GSM9075548 IBs-A0317DIPG PDOX model treated with abemaciclib, temozolomide, and radiation
- GSM9075549 IBs-9119DIPG PDOX model under control group
- GSM9075550 IBs-9119DIPG PDOX model treated with abemaciclib
- GSM9075551 IBs-9119DIPG PDOX model treated with radiation
- GSM9075552 IBs-9119DIPG PDOX model treated with temozolomide and radiation
- GSM9075553 IBs-9119DIPG PDOX model treated with abemaciclib and radiation
- GSM9075554 IBs-9119DIPG PDOX model treated with abemaciclib, temozolomide, and radiation
- GSM9075555 Primary DIPG biopsy sample
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