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| 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
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| 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.
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| 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.
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| 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 |
| E-mail(s) |
isabelle.leroux@icm-institute.org
|
| Organization name |
Paris Brain Institute
|
| Street address |
47 Boulevard de l'Hôpital
|
| City |
Paris |
| ZIP/Postal code |
75013 |
| Country |
France |
| |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (18)
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| This SubSeries is part of SuperSeries: |
| GSE168040 |
Cellular senescence in malignant cells promotes tumorigenesis in mouse and patient glioblastoma. |
|
| Relations |
| BioProject |
PRJNA705941 |
| SRA |
SRP308831 |
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