|
| Status |
Public on Apr 14, 2014 |
| Title |
Reconstructing and reprogramming the tumor propagating potential of glioblastoma stem-like cells: RNA-seq |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on a cellular hierarchy reminiscent of normal development but superimposed on underlying genetic aberrations. In glioblastoma (GBM), a subset of stem-like tumor- propagating cells (TPCs) appears to drive tumor progression and underlie therapeutic resistance, yet remain poorly understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2, SALL2, OLIG2) essential for GBM propagation. These TFs coordinately bind and activate TPC-specific regulatory elements, and are sufficient to fully reprogram differentiated GBM cells to ‘induced’ TPCs that recapitulate the epigenetic landscape and phenotype of native TPCs. We reconstruct a TF network model that highlights critical interactions and identifies novel therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in a devastating malignancy, provides detailed insight into the underlying gene regulatory programs, and suggests attendant therapeutic strategies.
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| |
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| Overall design |
3'end RNA sequencing
Submitter declares that the raw data are being deposited in dbGaP.
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| |
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| Contributor(s) |
Suvà ML, Rheinbay E, Gillespie SM, Bernstein BE |
| Citation(s) |
24726434 |
| Submission date |
Feb 07, 2014 |
| Last update date |
Jun 07, 2020 |
| Contact name |
Esther Rheinbay |
| E-mail(s) |
esther@broadinstitute.org
|
| Organization name |
Broad Institute
|
| Street address |
7 Cambridge Center
|
| City |
Cambridge |
| State/province |
MA |
| ZIP/Postal code |
02142 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (23)
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| This SubSeries is part of SuperSeries: |
| GSE54792 |
Epigenomic profiling of stemness, differentiation and primary tissues in human glioblastoma |
|
| Relations |
| BioProject |
PRJNA237655 |
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