|
| Status |
Public on May 28, 2013 |
| Title |
DNA methylation profiling of glioblastoma cancer stem cells |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by array
|
| Summary |
Glioblastoma (GBM) is thought to be driven by a sub-population of cancer stem cells (CSCs) that self-renew and recapitulate tumor heterogeneity, yet remain poorly understood. Here we present a comparative epigenomic analysis of GBM CSCs that reveals widespread activation of genes normally held in check by Polycomb repressors. These activated targets include a large set of developmental transcription factors (TFs) whose coordinated activation is unique to the CSCs. We demonstrate that a critical factor in the set, ASCL1, activates Wnt signaling by repressing the negative regulator DKK1. We show that ASCL1 is essential for maintenance and in vivo tumorigenicity of GBM CSCs. Genomewide binding profiles for ASCL1 and the Wnt effector LEF1 provide mechanistic insight and suggest widespread interactions between the TF module and the signaling pathway. Our findings demonstrate regulatory connections between ASCL1, Wnt signaling and collaborating TFs that are essential for the maintenance and tumorigenicity of GBM CSCs.
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| |
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| Overall design |
Epigenomic profiling of glioblastoma stem cells
|
| |
|
| Contributor(s) |
Rheinbay E, Chi AS, Bernstein BE |
| Citation(s) |
23707066 |
| Submission date |
Apr 12, 2013 |
| Last update date |
Jan 02, 2015 |
| 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 (1) |
| GPL8490 |
Illumina HumanMethylation27 BeadChip (HumanMethylation27_270596_v.1.2) |
|
| Samples (6)
|
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| This SubSeries is part of SuperSeries: |
| GSE46016 |
Epigenomic profiling of glioblastoma stem cells |
|
| Relations |
| BioProject |
PRJNA196903 |
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