E-GEOD-54047 - Reconstructing and reprogramming the tumor propagating potential of glioblastoma stem-like cells: ChIP-seq

Status
Released on 10 April 2014, last updated on 3 June 2014
Organism
Homo sapiens
Samples (26)
Protocols (3)
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. Histone modification profiling for H3K27ac and transcription factors in glioblastoma cell line reprogramming
Experiment type
ChIP-seq 
Contacts
Esther Rheinbay <esther@broadinstitute.org>, B E Bernstein, E Rheinbay, M L Suvà, S M Gillespie
MINSEQE
Exp. designProtocolsVariablesProcessedSeq. reads
Files
Links