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Phenotypic Plasticity of Invasive Edge Glioma Stem-like Cells in Response to Ionizing Radiation.

Cell reports | 2019

Unresectable glioblastoma (GBM) cells in the invading tumor edge can act as seeds for recurrence. The molecular and phenotypic properties of these cells remain elusive. Here, we report that the invading edge and tumor core have two distinct types of glioma stem-like cells (GSCs) that resemble proneural (PN) and mesenchymal (MES) subtypes, respectively. Upon exposure to ionizing radiation (IR), GSCs, initially enriched for a CD133+ PN signature, transition to a CD109+ MES subtype in a C/EBP-β-dependent manner. Our gene expression analysis of paired cohorts of patients with primary and recurrent GBMs identified a CD133-to-CD109 shift in tumors with an MES recurrence. Patient-derived CD133-/CD109+ cells are highly enriched with clonogenic, tumor-initiating, and radiation-resistant properties, and silencing CD109 significantly inhibits these phenotypes. We also report a conserved regulation of YAP/TAZ pathways by CD109 that could be a therapeutic target in GBM.

Pubmed ID: 30759398 RIS Download

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: R01 NS083767
  • Agency: NIGMS NIH HHS, United States
    Id: P30 GM124166
  • Agency: NCI NIH HHS, United States
    Id: P30 CA016672
  • Agency: NCI NIH HHS, United States
    Id: P01 CA069246
  • Agency: NCI NIH HHS, United States
    Id: R21 CA175875
  • Agency: NCI NIH HHS, United States
    Id: R01 CA201402
  • Agency: NCI NIH HHS, United States
    Id: P30 CA013148
  • Agency: NCI NIH HHS, United States
    Id: R01 CA183991
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS093843
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS087913
  • Agency: NCI NIH HHS, United States
    Id: P01 CA163205
  • Agency: NLM NIH HHS, United States
    Id: R00 LM011673
  • Agency: NINDS NIH HHS, United States
    Id: R01 NS095634
  • Agency: NCI NIH HHS, United States
    Id: R21 CA209345

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


ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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R Project for Statistical Computing (tool)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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SPSS (tool)

RRID:SCR_002865

Software package used for interactive, or batched, statistical analysis in social science, health sciences and marketing. Software platform offers advanced statistical analysis, a library of machine-learning algorithms, text analysis, open-source extensibility, integration with big data and deployment into applications.Versions that were produced by SPSS Inc. before the IBM acquisition (Versions 18 and earlier) would be given origin or publisher of SPSS Inc. in Chicago.

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Ivy Glioblastoma Atlas Project (tool)

RRID:SCR_005044

Platform for exploring the anatomic and genetic basis of glioblastoma at the cellular and molecular levels that includes two interactive databases linked together by de-identified tumor specimen numbers to facilitate comparisons across data modalities: * The open public image database, here, providing in situ hybridization data mapping gene expression across the anatomic structures inherent in glioblastoma, as well as associated histological data suitable for neuropathological examination * A companion database (Ivy GAP Clinical and Genomic Database) offering detailed clinical, genomic, and expression array data sets that are designed to elucidate the pathways involved in glioblastoma development and progression. This database requires registration for access. The hope is that researchers all over the world will mine these data and identify trends, correlations, and interesting leads for further studies with significant translational and clinical outcomes. The Ivy Glioblastoma Atlas Project is a collaborative partnership between the Ben and Catherine Ivy Foundation, the Allen Institute for Brain Science and the Ben and Catherine Ivy Center for Advanced Brain Tumor Treatment.

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Bioconductor (tool)

RRID:SCR_006442

Software repository for R packages related to analysis and comprehension of high throughput genomic data. Uses separate set of commands for installation of packages. Software project based on R programming language that provides tools for analysis and comprehension of high throughput genomic data.

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FlyBase (tool)

RRID:SCR_006549

Database of Drosophila genetic and genomic information with information about stock collections and fly genetic tools. Gene Ontology (GO) terms are used to describe three attributes of wild-type gene products: their molecular function, the biological processes in which they play a role, and their subcellular location. Additionally, FlyBase accepts data submissions. FlyBase can be searched for genes, alleles, aberrations and other genetic objects, phenotypes, sequences, stocks, images and movies, controlled terms, and Drosophila researchers using the tools available from the "Tools" drop-down menu in the Navigation bar.

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KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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BD Biosciences (tool)

RRID:SCR_013311

An Antibody supplier

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Cluster (tool)

RRID:SCR_013505

Software R package. Methods for Cluster analysis. Performs variety of types of cluster analysis and other types of processing on large microarray datasets.

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Microsoft Excel (tool)

RRID:SCR_016137

Software application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.

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Fiji (tool)

RRID:SCR_002285

Software package as distribution of ImageJ and ImageJ2 together with Java, Java3D and plugins organized into coherent menu structure. Used to assist research in life sciences.

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Primer3Plus (tool)

RRID:SCR_003081

A web interface to the Primer3 primer design program as an enhanced alternative for the CGI- scripts that come with Primer3.

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PeproTech (tool)

RRID:SCR_006802

An Antibody supplier

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FlowJo (tool)

RRID:SCR_008520

Software for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.

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CONTRA (tool)

RRID:SCR_010814

A tool for copy number variation (CNV) detection for targeted resequencing data such as those from whole-exome capture data.

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Vector BioLabs (tool)

RRID:SCR_011010

Biotechnology company focused on developing robust gene delivery products, by using its proprietary technologies. Since 2004, we have worked with over 300 research labs in 20 different countries to provide gene delivery products and services using many viral platforms including recombinant adenoviruses, adeno-associated virus (AAV) and lentivirus.

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Adobe Photoshop (tool)

RRID:SCR_014199

Software for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.

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HEK293-FT (tool)

RRID:CVCL_6911

Cell line HEK293-FT is a Transformed cell line with a species of origin Homo sapiens (Human)

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CEBP Beta antibody [1H7] (antibody)

RRID:AB_301598

This monoclonal targets CEBP Beta antibody [1H7]

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Anti-RalDH3 (antibody)

RRID:AB_2783547

This polyclonal targets RalDH3/ALDH1A3

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Human/Mouse/Rat Histone H2AX MAb (Clone 322105) (antibody)

RRID:AB_2114988

This monoclonal targets Human/Mouse/Rat Histone H2AX MAb (Clone 322105)

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p21 (DCS-60) (antibody)

RRID:AB_785023

This monoclonal targets Human CDKN1A

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GAPDH antibody (antibody)

RRID:AB_307273

This polyclonal targets GAPDH

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c-Myc Antibody (9E10) (antibody)

RRID:AB_627268

This monoclonal targets c-Myc

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Anti-β-Actin Antibody (C4) (antibody)

RRID:AB_626632

This monoclonal targets β-Actin

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N-Cadherin (antibody)

RRID:AB_2077527

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RRID:AB_570666

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Phospho-YAP (Ser127) (D9W2I) Rabbit mAb (antibody)

RRID:AB_2650553

This recombinant monoclonal targets YAP

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CD44 Antibody (antibody)

RRID:AB_2076463

This polyclonal targets CD44

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YAP/TAZ (D24E4) Rabbit mAb (antibody)

RRID:AB_10950494

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Mouse IgG1 Isotype Control (Clone 11711) (antibody)

RRID:AB_357344

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CD109 (C-9) (antibody)

RRID:AB_10610041

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Human/Mouse CD109 Phycoerythrin MAb (Clone 496920) (antibody)

RRID:AB_10643402

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CD133/1 (AC133)-APC, human (antibody)

RRID:AB_244340

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RRID:AB_2783547

This polyclonal targets RalDH3/ALDH1A3

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RRID:AB_570666

This polyclonal targets Oligodendrocute transcription factor 2

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CEBP Beta antibody [1H7] (antibody)

RRID:AB_301598

This monoclonal targets CEBP Beta antibody [1H7]

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