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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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