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Series GSE260933 Query DataSets for GSE260933
Status Public on May 01, 2024
Title Mutant IDH inhibitors induce lineage differentiation in IDH-mutant Oligodendroglioma II
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary A subset of patients with IDH-mutant glioma respond to inhibitors of mutant IDH (IDHi), yet the molecular underpinnings of such responses are not understood. Here, we profiled by single-cell or single-nucleus RNA-sequencing three IDH-mutant oligodendrogliomas from patients who derived clinical benefit from IDHi. Importantly, the tissues were sampled on-drug, four weeks from treatment initiation. We further integrate our findings with analysis of single-cell and bulk transcriptomes from independent cohorts and experimental models. We find that IDHi treatment induces a robust differentiation towards the astrocytic lineage, accompanied by a depletion of stem-like cells and a reduction of cell proliferation. Furthermore, mutations in NOTCH1 are associated with decreased astrocytic differentiation and may limit the response to IDHi. Our study highlights the differentiating potential of IDHi on the cellular hierarchies that drive oligodendrogliomas and suggests a genetic modifier that may improve patient stratification.
 
Overall design Fresh or frozen IDH-mutant gliomas treated with IDHi were dissociated and profiled by single-cell or single-nucleus RNA sequencing (Smart-seq2 or 10x). In-vitro IDH-mutant glioma models treated with or without IDHi was profiled by single-cell RNA-seq (10x) and single-cell multi-omics protocol (DNA methylome and transcriptome). In-vitro IDH-mutant glioma models that we knock out Notch1 (Notch1-KO) and the control (Notch1-WT) were profiled by single-cell RNA-sequencing (10x).
 
Contributor(s) Spitzer A, Gritsch S, Nomura M, Ligon KL, Cahill DP, Suva M, Tirosh I
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Submission date Mar 05, 2024
Last update date May 01, 2024
Contact name Masashi Nomura
E-mail(s) masashin0914@hotmail.com
Organization name Massachusetts General Hospital
Department Pathology
Street address 149 13th street
City Charlestown
State/province MA
ZIP/Postal code 02129
Country USA
 
Platforms (1)
GPL30172 NextSeq 2000 (Mus musculus)
Samples (141)
GSM8128224 AGI881_P1_A01, scRRBS (multi-omics)
GSM8128225 AGI881_P1_B06, scRRBS (multi-omics)
GSM8128226 AGI881_P1_A03, scRRBS (multi-omics)
Relations
BioProject PRJNA1084066

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE260933_scRRBS_mouse_multiomics_processed_CpG.tsv.gz 20.9 Mb (ftp)(http) TSV
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