Genome-wide analysis of GBM-derived brain tumor stem cells-like (BTSCs)
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE137310 | GEO | 2019/09/13
REPOSITORIES: GEO
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Project description:Genome-wide analysis of GBM-derived brain tumor stem cells-like (BTSCs)
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Project description:The principle of tumor growth is one of the most fundamental aspects in cancer biology and it remains to be superficially understood. Here we developed a set of genetic and mathematical tools for integrative analysis of mouse glioblastoma (GBM) progression. Quantitative temporal imaging of mouse GBM and mathematical modeling suggest that mouse GBM grows exponentially, which led to the discovery that a sustainable exponential growth requires outward migrating brain tumor stem cells (BTSCs). Quantitative single cell tracing of BTSCs in vivo unravels symmetric expansion of BTSCs, asymmetric differentiation, and a non-reversible differentiation process during tumor progression. Mosaic tracing of BTSCs and non-BTSCs reveals cellular dynamic changes and turnover. These experimentally collected parameters were integrated step by step to a quantitative mathematical model of GBM growth, which faithfully predicts tumor cellular architecture, tumor response to chemotherapy and BTSC therapy. Bulk and single cell RNA-Seq reveals distinct molecular hierarchy and molecular heterogeneity in BTSCs, which was confirmed by analyzing human GBM single-cell RNA-Seq results. This study reveals fundamental developmental principles that govern tumor growth, which provides insights into understanding cancer development, tumor heterogeneity and GBM therapy.
2022-02-02 | GSE126212 | GEO
Project description:Principle of tumor growth is one fundamental aspect of cancer biology and it remains to be superficially understood. Here we developed a set of genetic and mathematic tools allow integrative analysis of mouse glioblastoma (GBM) progression. Quantitative temporal imaging of mouse GBM and mathematic modeling suggest that mouse GBM grows exponentially, which led to the discovery that a sustainable exponential growth requires outward migrating brain tumor stem cells (BTSCs). Quantitative single cell tracing of BTSCs in vivo unravels symmetric expansion of BTSCs, asymmetric differentiation, and a non-reversible differentiation process during tumor progression. Mosaic tracing of BTSCs and non-BTSCs reveals a cellular temporal dynamic changes and cellular turnover. These experimentally collected parameters were integrated step by step to a quantitative mathematic model of GBM growth, which faithfully predicts tumor cellular architecture, tumor response to chemotherapy and BTSC therapy. Bulk and single cell RNA-Seq reveals distinct molecular hierarchy and molecular heterogeneity in BTSCs, which was confirmed by analyzing human GBM single cell RNA-Seq results. This study reveals basic developmental principles that govern tumor development, which provides novel understanding of cancer development, tumor heterogeneity and new approaches to treat GBM.
2024-05-01 | GSE114456 | GEO
Project description:This SuperSeries is composed of the following subset Series: GSE24446: Genetic abnormalities in GBM brain tumors GSE24452: Genetic abnormalities in various cell subpopulations of GBM brain tumors GSE24557: Exon-level expression profiles of GBM brain tumors Refer to individual Series
2010-11-21 | E-GEOD-24558 | biostudies-arrayexpress
Project description:Cancer cells can metabolize glutamine to replenish TCA cycle intermediates, leading to a dependence on glutaminolysis for cell survival. However, a mechanistic understanding of the role that glutamine metabolism has on the survival of glioblastoma (GBM) brain tumor stem cells (BTSCs) has not yet been elucidated. Here we report that, across a panel of twenty glioblastoma BTSC lines, glutaminase (GLS) inhibition showed a variable response – from complete blockade of cell growth to absolute resistance. Surprisingly, BTSC sensitivity to GLS inhibition was a result of reduced intracellular glutamate triggering the amino acid deprivation response (AADR) and not due to the contribution of glutaminolysis to the TCA cycle. Moreover, BTSC sensitivity to GLS inhibition negatively correlated with the expression of the astrocytic glutamate transporters EAAT1 and EAAT2. Blocking glutamate transport in BTSCs with high EAAT1/EAAT2 expression rendered these cells susceptible to GLS inhibition, triggering the AADR, and limiting cell growth. These findings uncover a unique metabolic vulnerability in BTSCs, support the therapeutic targeting of the upstream activators and downstream effectors of the AADR pathway in GBM, and demonstrate that gene expression patterns reflecting the cellular hierarchy of the tissue of origin can alter the metabolic requirements of the cancer stem cell population.
2020-12-25 | GSE155300 | GEO
Project description:Sixteen paired matched samples from primary breast cancers and brain metastases diagnosed between April 1, 2001 and December 31, 2012 were collected from 8 institutions. Brain metastases were identified based on magnetic resonance imaging and/or computed tomography findings. The clinical characteristics of all the patients were obtained from their medical records. This study was approved by the institutional review board of each participating institute (Tokai University School of Medicine; National Hospital Organization Osaka National Hospital; Kinki University School of Medicine; Niigata Cancer Center Hospital; Shizuoka General Hospital; Hokkaido Cancer Center; National Hospital Organization, Tokyo Medical Center; and Gunma Prefectural Cancer Center). Matching primary breast cancers and brain metastases Formalin-Fixed Paraffin-Embedded (FFPE) specimens for gene expression analysis were collected into RNA. RNA from specimens was isolated, and quantity and quality of the each RNA was using an Agilent 2100 Bioanalyzer (Agilent Technologies). Genome-wide expression levels of transcripts were analyzed using the Affymetrix U133A gene chips (Affymetrix) according to the manufacture’s instructions.
2019-09-25 | GSE125989 | GEO
Project description:We have developed a nonheuristic genome topography scan (GTS) algorithm to characterize the patterns of genomic alterations in human glioblastoma (GBM), identifying frequent p18INK4C and p16INK4A codeletion. Functional reconstitution of p18INK4C in GBM cells null for both p16INK4A and p18INK4C resulted in impaired cell-cycle progression and tumorigenic potential. Conversely, RNAi-mediated depletion of p18INK4C in p16INK4A-deficient primary astrocytes or established GBM cells enhanced tumorigenicity in vitro and in vivo. Furthermore, acute suppression of p16INK4A in primary astrocytes induced a concomitant increase in p18INK4C. Together, these findings uncover a feedback regulatory circuit in the astrocytic lineage and demonstrate a bona fide tumor suppressor role for p18INK4C in human GBM wherein it functions cooperatively with other INK4 family members to constrain inappropriate proliferation. Keywords: comparative genomic hybridization DNA copy number abberation of human glioblastoma tumors were obtained by comparative genomic hybridization of GBM tumor vs. normal human DNA. 11 human GBM samples were analyzed on Agilent human 244A human cgh array (G4411B). Normal Human DNA was used as reference. Some samples were hybridized with dye-swap replica.
2008-04-29 | E-GEOD-9177 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of GBM xenografts. The Illumina EPIC 850k Human DNA methylation array used to obtain DNA methylation profiles across approximately 800,000 CpGs in GBM xenograft samples. Samples included xx GBM xenografts.
2019-06-26 | GSE132650 | GEO
Project description:GBM is a heterogenous tumor. Based on membrane protein expression, the GBM single cell dissociates were seperated into different subfractions by FACS assay. The genomic aberration among each populations were compared by analysis of CGH data. Genomic DNA were extracted from sorted cell population and CGH assay were performed to compare the similarity genomic abnormality among different cell groups.
2010-11-21 | E-GEOD-24452 | biostudies-arrayexpress
Project description:Our adult GBM patient-derived xenograft mouse models keep the genomics characteristics of GBM patient tumors.
2023-07-12 | GSE207886 | GEO