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Publication

Genome-Wide CRISPR-Cas9 Screens Expose Genetic Vulnerabilities and Mechanisms of Temozolomide Sensitivity in Glioblastoma Stem Cells.

Cell reports | 2019

Glioblastoma therapies have remained elusive due to limitations in understanding mechanisms of growth and survival of the tumorigenic population. Using CRISPR-Cas9 approaches in patient-derived GBM stem cells (GSCs) to interrogate function of the coding genome, we identify actionable pathways responsible for growth, which reveal the gene-essential circuitry of GBM stemness and proliferation. In particular, we characterize members of the SOX transcription factor family, SOCS3, USP8, and DOT1L, and protein ufmylation as important for GSC growth. Additionally, we reveal mechanisms of temozolomide resistance that could lead to combination strategies. By reaching beyond static genome analysis of bulk tumors, with a genome-wide functional approach, we reveal genetic dependencies within a broad range of biological processes to provide increased understanding of GBM growth and treatment resistance.

Pubmed ID: 30995489 RIS Download

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Associated grants

Agency: NCI NIH HHS, United States
Id: P30 CA016672
Agency: CIHR, Canada

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This is a list of tools and resources that we have found mentioned in this publication.

Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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Mendeley Data (tool)

RRID:SCR_002750

A free reference manager and academic social network to organize your research, collaborate with others online, and discover the latest research. Automatically generate bibliographies, Collaborate easily with other researchers online, Easily import papers from other research software, Find relevant papers based on what you're reading, Access your papers from anywhere online, Read papers on the go with the iPhone app. The software, Mendeley Desktop, offers: * Automatic extraction of document details * Efficient management of your papers * Sharing and synchronization of your library (or parts of it) * Additional features: A plug-in for citing your articles in Microsoft Word, OCR (image-to-text conversion, so you can full-text search all your scanned PDFs), etc The website, Mendeley Web, complements Mendeley Desktop by offering these features: * An online back up of your library * Statistics of all things interesting * A research network that allows you to keep track of your colleagues' publications, conference participations, awards etc * A recommendation engine for papers that might interest you

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Cytoscape (tool)

RRID:SCR_003032

Software platform for complex network analysis and visualization. Used for visualization of molecular interaction networks and biological pathways and integrating these networks with annotations, gene expression profiles and other state data.

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PRISM (tool)

RRID:SCR_005375

THIS RESOURCE IS NO LONGER IN SERVICE. Documented on May 5,2022.Tool that predicts interactions between transcription factors and their regulated genes from binding motifs. Understanding vertebrate development requires unraveling the cis-regulatory architecture of gene regulation. PRISM provides accurate genome-wide computational predictions of transcription factor binding sites for the human and mouse genomes, and integrates the predictions with GREAT to provide functional biological context. Together, accurate computational binding site prediction and GREAT produce for each transcription factor: 1. putative binding sites, 2. putative target genes, 3. putative biological roles of the transcription factor, and 4. putative cis-regulatory elements through which the factor regulates each target in each functional role.

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