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Series GSE199110 Query DataSets for GSE199110
Status Public on Jan 26, 2023
Title WDR5 represents a therapeutically exploitable target for cancer stem cells in glioblastoma
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors that are driven by populations of cancer stem cells (CSCs). Despite their importance for tumor growth, few molecular mechanisms critical for CSC population maintenance have been exploited for therapeutic development. We developed a spatially resolved loss-of-function screen in GBM patient-derived organoids to identify essential epigenetic regulators in the SOX2-enriched, therapy resistant niche and identified WDR5 as indispensable for this population. WDR5 is a component of the WRAD complex, which promotes SET1-family-mediated Lys4 methylation of histone H3, associated with positive regulation of transcription. Genetic and pharmacologic inhibition of WDR5 reduced growth and self-renewal of CSCs as well as CSC-mediated tumor growth. Further, WDR5 inhibitors blocked WRAD complex assembly, reduced H3K4 trimethylation, and inhibited tumor growth. These findings highlight the role of WDR5 and the WRAD complex for maintaining the CSC state and provide a rationale for therapeutic development of WDR5 inhibitors for GBM and other advanced cancers.
 
Overall design CUT&Tag data from 4 replicates each for DMSO and WDR5 WIN site inhibitor (C16)
 
Contributor(s) Mitchell K, Shakya S, Arora S, Silver DJ, Goins CM, Wallace L, Roversi G, Schafer R, Kay K, Miller TE, Lauko A, Bassett J, D'Amato Kass J, Kashyap A, Mulkearns-Hubert EE, Johnson S, Alvarado J, Rich JN, Paddison PJ, Patel AP, Stauffer SR, Hubert CG, Lathia JD
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Submission date Mar 21, 2022
Last update date Jan 29, 2023
Contact name Sonali Arora
E-mail(s) sarora@fredhutch.org
Organization name FHCRC
Street address 1100 Fairview Ave N,
City Seattle
State/province WA
ZIP/Postal code 98109
Country USA
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (8)
GSM5964513 DI318 CSCs + DMSO rep1
GSM5964514 DI318 CSCs + DMSO rep2
GSM5964515 DI318 CSCs + DMSO rep3
Relations
BioProject PRJNA818419

Download family Format
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE199110_RAW.tar 4.4 Mb (http)(custom) TAR (of NARROWPEAK)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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