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Series GSE74557 Query DataSets for GSE74557
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
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.
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
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
Organization name MGH
Department Molecular Pathology
Lab Bernstein
Street address 165 Cambridge Street
City Boston
ZIP/Postal code 02114
Country USA
Platforms (1)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (44)
GSM1922941 Input_GSC8Per_ChIPseq
GSM1922942 Input_GSC8_4d-das_ChIPseq
GSM1922943 Input_GSC8_12d-das_ChIPseq
BioProject PRJNA300725
SRA SRP091435

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Supplementary file Size Download File type/resource
GSE74557_RAW.tar 5.5 Gb (http)(custom) TAR (of BW, TXT)
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Processed data provided as supplementary file
Raw data are available in SRA

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