{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Mitchell K"],"funding":["National Center for Advancing Translational Sciences","National Institute of Neurological Disorders and Stroke","NCATS NIH HHS","American Brain Tumor Association Discovery","VeloSano Cancer Research Fund","Clinical and Translational Science Award","Clinical Translational Science Collaborative of Cleveland","National Institutes of Health","NIH","American Cancer Society Institutional Research Grant","American Cancer Society","NCI","Lerner Research Institute","NIDDK NIH HHS","Case Comprehensive Cancer Center","National Cancer Institute","NCI NIH HHS","NINDS NIH HHS","NIGMS NIH HHS"],"pagination":["86-102"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10069451"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["37(3-4)"],"pubmed_abstract":["Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors driven by populations of cancer stem cells (CSCs). However, 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 (H3K4me), associated with positive regulation of transcription. In GBM CSCs, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogeni"],"journal":["Genes & development"],"pubmed_title":["WDR5 represents a therapeutically exploitable target for cancer stem cells in glioblastoma."],"pmcid":["PMC10069451"],"funding_grant_id":["IRG-16-186-21","K00 CA253768","UL1 TR002548","R35 CA197718","KL2 TR002547","T32 GM007250","F30 CA250254","P30 DK020593","F32 NS116109","R35 NS127083","P01 CA245705","T32 CA059366","RES513876"],"pubmed_authors":["Wallace L","Alvarado J","Kashyap A","Schafer RE","Lauko A","Johnson S","Stauffer SR","D'Amato Kass J","Silver DJ","Goins CM","Bassett J","Holland EC","Mitchell K","Roversi G","Kay K","Rich JN","Miller TE","Patel AP","Arora S","Mulkearns-Hubert EE","Shakya S","Hubert CG","Paddison PJ","Sprowls SA","Lathia JD"],"additional_accession":[]},"is_claimable":false,"name":"WDR5 represents a therapeutically exploitable target for cancer stem cells in glioblastoma.","description":"Glioblastomas (GBMs) are heterogeneous, treatment-resistant tumors driven by populations of cancer stem cells (CSCs). However, 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 (H3K4me), associated with positive regulation of transcription. In GBM CSCs, WDR5 inhibitors blocked WRAD complex assembly and reduced H3K4 trimethylation and expression of genes involved in CSC-relevant oncogeni","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2025-04-04T22:47:54.409Z","creation":"2025-04-04T22:47:54.409Z"},"accession":"S-EPMC10069451","cross_references":{"pubmed":["36732025"],"doi":["10.1101/gad.349803.122"]}}