Reconstructing and Reprogramming the Tumor-Propagating Potential of Glioblastoma Stem-like Cells
作者： Mario L. Suvà , Esther Rheinbay , Shawn M. Gillespie , Anoop P. Patel , Hiroaki Wakimoto
DOI: 10.1016/J.CELL.2014.02.030
关键词: Enhancer 、 Tumor progression 、 Biology 、 Genetics 、 Chromatin 、 Reprogramming 、 Transcription factor 、 Stem cell 、 Epigenetics 、 SOX2 、 Neuroscience
摘要: Summary 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 cellular hierarchies reminiscent of normal development but superimposed underlying genetic aberrations. In glioblastoma (GBM), a subset stem-like tumor-propagating cells (TPCs) appears drive tumor progression and underlie therapeutic resistance yet remain poorly understood. Here, we identify core set neurodevelopmental TFs (POU3F2, SOX2, SALL2, OLIG2) essential for GBM propagation. These coordinately bind activate TPC-specific regulatory sufficient fully reprogram differentiated "induced" TPCs, recapitulating the epigenetic landscape phenotype native TPCs. We reconstruct network model highlights critical interactions identifies candidate targets eliminating Our study establishes basis developmental hierarchy in GBM, provides detailed insight into gene programs, suggests attendant strategies. PaperClip
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