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| Status |
Public on Jan 25, 2017 |
| Title |
Adaptive chromatin remodeling in glioblastoma stem cell plasticity and drug tolerance |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
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| Summary |
Many cancers are postulated to harbor developmental hierarchies in which cells display variability in stem-like character, tumor propagating ability, and proliferation. In glioblastoma (GBM), glioma stem cells (GSCs) reside atop such a tumor cellular hierarchy, and are thought to resist current therapies and thus underlie inevitable relapse. Here we show that GSCs can evade RTK inhibition by reversibly regressing to a slow-cycling state reminiscent of quiescent neural stem cells. This process involves up-regulation of numerous histone demethylases, including KDM6A/B, which remodel the chromatin landscape and are selectively essential for drug persister survival. Chromatin remodeling is accompanied by activation of various neurodevelopmental master regulators and Notch signaling, changes which closely parallel critical aspects of neural stem cell biology. Thus our findings illustrate how cancer cells may hijack native developmental programs for deranged proliferation, adaptation, and tolerance in the face of stress. Our studies highlight key roles for chromatin remodeling and developmental plasticity in GBM biology, and suggest strategies for overcoming therapeutic resistance by targeting epigenetic and developmental pathways.
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| Overall design |
ChIP-seq for histone modifications and Notch factors in glioblastoma stem cell lines with various drug treatments
RNA-seq in glioblastoma stem cell lines with various drug treatments
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| Contributor(s) |
Sievers C, Liau B, Bernstein B |
| Citation(s) |
27989769 |
| Submission date |
Nov 01, 2015 |
| Last update date |
May 15, 2019 |
| Contact name |
Cem Sievers |
| E-mail(s) |
csievers@mgh.harvard.edu
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| Organization name |
MGH
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| Department |
Molecular Pathology
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| Lab |
Bernstein
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| Street address |
165 Cambridge Street
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| City |
Boston |
| ZIP/Postal code |
02114 |
| Country |
USA |
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| Platforms (1) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (44)
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| Relations |
| BioProject |
PRJNA300725 |
| SRA |
SRP091435 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE74557_RAW.tar |
5.5 Gb |
(http)(custom) |
TAR (of BW, TXT) |
SRA Run Selector |
| Processed data provided as supplementary file |
| Raw data are available in SRA |
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