GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
Series GSE168037 Query DataSets for GSE168037
Status Public on Dec 15, 2022
Title Cellular senescence in malignant cells promotes tumorigenesis in mouse and patient glioblastoma [bulk RNA-seq]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary GBM mouse model: The goal of this study is to compare the transcriptomic landscape at the endpoint of GBMs upon senescent cells deletion. We introduced the p16-3MR transgene in the GBM mouse model to selectively delete senescent cells expressing high level of p16Ink4a (p16Ink4a Hi) upon ganciclovir (GCV) injection. We compared p16-3MR+GCV GBMs to two control conditions, either WT+GCV or p16-3MR+GCV. We showed a slight decreased of p16Ink4a transcripts in p16-3MR+GCV compared to WT+GCV GBMs and GSEA demonstrated significant down-regulation of senescence pathways in p16-3MR+GCV GBMs compared to control GBMs.
GBM-derived organoids: We used a mouse GBM-derived organoids model to further explore the function of Nrf2, that we identified as one potential trigger of the pro-tumoral action of p16Ink4a Hi malignant cells. We compared GBM-derived organoids treated with the senolytic ABT263 (Navitoclax; inhibitor of the anti-apoptotic proteins Blcl2 and BCL-xL) or vehicle (vhc) after 14 days in culture. We validated ABT263 efficacy via the significant downregulation of the expression of p16Ink4a, p15Ink4b and p21Cip1 senescent markers. We further identified upon senolytic treatment, downregulated genes encoding for SASP. Importantly, GSEA revealed a significant downregulation of Nrf2 pathway upon senolytic treatment.
Overall design GBM mouse model: Bulk RNAseq on WT+GCV, p16-3MR+vhc and p16-3MR+GCV mouse GBMs at end timepoints.
GBM-derived organoids: Bulk RNAseq on GBM-derived organoids treated with ABT263 (2µM) or vhc.
Contributor(s) Le Roux I, Salam R, Guégan J, Bertrand M
Citation(s) 36707509
Submission date Mar 02, 2021
Last update date Feb 10, 2023
Contact name Isabelle Leroux
Organization name Paris Brain Institute
Street address 47 Boulevard de l'Hôpital
City Paris
ZIP/Postal code 75013
Country France
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (18)
GSM5124259 WT+GCV_747
GSM5124260 WT+GCV_763
GSM5124261 WT+GCV_880
This SubSeries is part of SuperSeries:
GSE168040 Cellular senescence in malignant cells promotes tumorigenesis in mouse and patient glioblastoma.
BioProject PRJNA705941
SRA SRP308831

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
GSE168037_RAW.tar 10.5 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap