NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE260997 Query DataSets for GSE260997
Status Public on May 01, 2024
Title Mutant IDH inhibitors induce lineage differentiation in IDH-mutant Oligodendroglioma III
Organisms Homo sapiens; Mus musculus
Experiment type Expression 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).

***************************************************************
human raw data not deposited due to patient privacy concerns
***************************************************************
 
Contributor(s) Spitzer A, Gritsch S, Nomura M, Ligon KL, Cahill DP, Suva M, Tirosh I
Citation missing Has this study been published? Please login to update or notify GEO.
Submission date Mar 06, 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 (2)
GPL30172 NextSeq 2000 (Mus musculus)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (2458)
GSM8129392 MGH170-P7-A01-CD45pos, Smart-seq2
GSM8129393 MGH170-P7-A02-CD45pos, Smart-seq2
GSM8129394 MGH170-P7-A03-CD45pos, Smart-seq2
Relations
BioProject PRJNA1084806

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
GSE260997_Smartseq2_Astrocytoma_processed_TPM.tsv.gz 16.3 Mb (ftp)(http) TSV
GSE260997_Smartseq2_Oligodendroglioma_processed_TPM.tsv.gz 15.7 Mb (ftp)(http) TSV
GSE260997_Smartseq2_mouse_multiomics_processed_TPM.tsv.gz 3.9 Mb (ftp)(http) TSV
SRA Run SelectorHelp
Raw data are available in SRA
| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap