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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Reconstructing and reprogramming the tumor propagating potential of glioblastoma stem-like cells: ChIP-seq

ABSTRACT: Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on a cellular hierarchy reminiscent of normal development but superimposed on underlying genetic aberrations. In glioblastoma (GBM), a subset of stem-like tumor- propagating cells (TPCs) appears to drive tumor progression and underlie therapeutic resistance, yet remain poorly understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2, SALL2, OLIG2) essential for GBM propagation. These TFs coordinately bind and activate TPC-specific regulatory elements, and are sufficient to fully reprogram differentiated GBM cells to ‘induced’ TPCs that recapitulate the epigenetic landscape and phenotype of native TPCs. We reconstruct a TF network model that highlights critical interactions and identifies novel therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in a devastating malignancy, provides detailed insight into the underlying gene regulatory programs, and suggests attendant therapeutic strategies. Histone modification profiling for H3K27ac and transcription factors in glioblastoma cell line reprogramming

ORGANISM(S): Homo sapiens

SUBMITTER: Esther Rheinbay

PROVIDER: E-GEOD-54047 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Reconstructing and reprogramming the tumor propagating potential of glioblastoma stem-like cells: RNA-seq

Project description:Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on a cellular hierarchy reminiscent of normal development but superimposed on underlying genetic aberrations. In glioblastoma (GBM), a subset of stem-like tumor- propagating cells (TPCs) appears to drive tumor progression and underlie therapeutic resistance, yet remain poorly understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2, SALL2, OLIG2) essential for GBM propagation. These TFs coordinately bind and activate TPC-specific regulatory elements, and are sufficient to fully reprogram differentiated GBM cells to ‘induced’ TPCs that recapitulate the epigenetic landscape and phenotype of native TPCs. We reconstruct a TF network model that highlights critical interactions and identifies novel therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in a devastating malignancy, provides detailed insight into the underlying gene regulatory programs, and suggests attendant therapeutic strategies. 3'end RNA sequencing

2014-04-14 | E-GEOD-54791 | biostudies-arrayexpress

Reconstructing and reprogramming the tumor propagating potential of glioblastoma stem-like cells: ChIP-seq

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DNA methylation profiling of glioblastoma cancer stem cells

Project description:Glioblastoma (GBM) is thought to be driven by a sub-population of cancer stem cells (CSCs) that self-renew and recapitulate tumor heterogeneity, yet remain poorly understood. Here we present a comparative epigenomic analysis of GBM CSCs that reveals widespread activation of genes normally held in check by Polycomb repressors. These activated targets include a large set of developmental transcription factors (TFs) whose coordinated activation is unique to the CSCs. We demonstrate that a critical factor in the set, ASCL1, activates Wnt signaling by repressing the negative regulator DKK1. We show that ASCL1 is essential for maintenance and in vivo tumorigenicity of GBM CSCs. Genomewide binding profiles for ASCL1 and the Wnt effector LEF1 provide mechanistic insight and suggest widespread interactions between the TF module and the signaling pathway. Our findings demonstrate regulatory connections between ASCL1, Wnt signaling and collaborating TFs that are essential for the maintenance and tumorigenicity of GBM CSCs. Epigenomic profiling of glioblastoma stem cells

2013-05-28 | E-GEOD-46015 | biostudies-arrayexpress

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-04-11 | E-GEOD-54792 | biostudies-arrayexpress

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2013-07-08 | E-GEOD-46439 | biostudies-arrayexpress

A Proneural to Mesenchymal Transition Mediated by NFkB Promotes Radiation Resistance in Glioblastoma (part 1)

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2013-08-15 | E-GEOD-49161 | biostudies-arrayexpress

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