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| Status |
Public on Jun 30, 2024 |
| Title |
Glioblastoma initiation, migration, and cell types are regulated by core bHLH transcription factors ASCL1 and OLIG2 [ChIP-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Glioblastomas (GBMs) are highly aggressive, infiltrative, and heterogeneous brain tumors driven by complex driver mutations and glioma stem cells (GSCs). The neurodevelopmental transcription factors ASCL1 and OLIG2 are co-expressed in GBMs, but their role in regulating the heterogeneity and hierarchy of GBM tumor cells is unclear. Here, we show that oncogenic driver mutations lead to dysregulation of ASCL1 and OLIG2, which function redundantly to initiate brain tumor formation in a mouse model of GBM. Subsequently, the dynamic levels and reciprocal binding of ASCL1 and OLIG2 to each other and to downstream target genes then determine the cell types and degree of migration of tumor cells. Single-cell RNA sequencing (scRNA-seq) reveals that a high level of ASCL1 is key in defining GSCs by upregulating a collection of ribosomal protein, mitochondrial, neural stem cell (NSC), and cancer metastasis genes – all essential for sustaining the high proliferation, migration, and therapeutic resistance of GSCs.
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| Overall design |
ChIP-seq assays for ASCL1 and OLIG2 binding were done using two orthotopic lines of patient-derived GBM xenografts (PDX-GBMs) (R548 and R738).
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| Contributor(s) |
Myers BL, Vue TY |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
Nov 16, 2023 |
| Last update date |
Jul 01, 2024 |
| Contact name |
Tou Yia Vue |
| E-mail(s) |
TVue@salud.unm.edu
|
| Organization name |
University of New Mexico Health Sciences Center
|
| Department |
Neurosciences
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| Lab |
Vue
|
| Street address |
915 Camino De Salud NE, Fitz Hall 145
|
| City |
Albuquerque |
| State/province |
New Mexico |
| ZIP/Postal code |
87131 |
| Country |
USA |
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| Platforms (1) |
| GPL10999 |
Illumina Genome Analyzer IIx (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA1041349 |
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