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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Sep 09, 2014 |
| Title |
Transformation of quiescent adult oligodendrocyte precursor cells into malignant glioma through a multi-step reactivation process |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
How malignant gliomas arise in a mature brain remains a mystery, hindering the development of preventive and therapeutic interventions. We previously showed that oligodendrocyte precursor cells (OPCs) can be transformed into glioma when mutations are introduced perinatally. However, adult OPCs rarely proliferate compared to their perinatal counterparts. Whether these relatively quiescent cells have the potential to transform is unknown, which is a critical question considering the late onset of human glioma. Additionally, the events taking place between initial mutation and a fully developed tumor mass (pre-malignant phase) are particularly poorly understood in glioma. Here we used a temporally controllable Cre transgene to delete p53 and NF1 specifically in adult OPCs, and demonstrated that these cells consistently give rise to malignant gliomas. To investigate the transforming process of quiescent adult OPCs, we then tracked these cells throughout the pre-malignant phase, which revealed a dynamic multi-step transformation, starting with rapid but transient hyper-proliferative reactivation, followed by a long period of dormancy, then final malignant transformation. Using pharmacological approaches, we discovered that mTOR signaling is critical for both the initial OPC reactivation step and late stage tumor cell proliferation, and thus might be a potential target for both glioma prevention and treatment. In summary, our results firmly establish the transforming potential of adult OPCs, and reveal an actionable multi-phasic reactivation process that turns slowly dividing OPCs into malignant gliomas.
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| Overall design |
44K Mouse Development Oligo Microarrays from Agilent Technologies were used for microarray analysis. For each experiment, total RNA was fluorescently labeled and hybridized directly against a common reference sample generated from the RNA pool of four WT P17 mouse brain neocortex.
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| Contributor(s) |
Galvao RP, Kasina A, McNeill RS, Harbin JE, Foreman O, Verhaak RG, Nishiyama A, Miller CR, Zong H |
| Citation(s) |
25246577 |
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| Submission date |
Sep 09, 2014 |
| Last update date |
Oct 01, 2014 |
| Contact name |
Rui Pedro Galvao |
| E-mail(s) |
galvao@uoregon.edu
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| Organization name |
University of Oregon
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| Street address |
1229 University of Oregon
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| City |
Eugene |
| State/province |
Oregon |
| ZIP/Postal code |
97403 |
| Country |
USA |
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| Platforms (1) |
| GPL19163 |
Agilent-015062 Mouse Dev Gene Expression Microarray (Probe name version) |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA260644 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE61282_RAW.tar |
66.5 Mb |
(http)(custom) |
TAR (of GPR) |
| Processed data included within Sample table |
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