Reconstructing and Reprogramming the Tumor-Propagating Potential of Glioblastoma Stem-like Cells
| العنوان: | Reconstructing and Reprogramming the Tumor-Propagating Potential of Glioblastoma Stem-like Cells |
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| المؤلفون: | Brian V. Nahed, Daniel P. Cahill, Miguel Rivera, Esther Rheinbay, Anoop P. Patel, Samantha Beik, Hiroaki Wakimoto, Bradley E. Bernstein, Orit Rozenblatt-Rosen, Anthony Wei Shine Chi, David N. Louis, Mario L. Suvà, Simon Kasif, Nikki E. Rossetti, Sabah Kadri, Robert L. Martuza, Shawn M. Gillespie, Aviv Regev, Ivo Wortman, Samuel D. Rabkin, Nicolo Riggi, Itay Tirosh, William T. Curry, Alex K. Shalek |
| المساهمون: | Massachusetts Institute of Technology. Department of Biology, Regev, Aviv |
| المصدر: | PMC |
| بيانات النشر: | Elsevier BV, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Nerve Tissue Proteins, Biology, Article, General Biochemistry, Genetics and Molecular Biology, Epigenesis, Genetic, SOX2, Cell Line, Tumor, Basic Helix-Loop-Helix Transcription Factors, Humans, Epigenetics, Regulatory Elements, Transcriptional, Enhancer, Transcription factor, Cells, Cultured, Genetics, Brain Neoplasms, Biochemistry, Genetics and Molecular Biology(all), Cell Differentiation, Oligodendrocyte Transcription Factor 2, Chromatin, Gene Expression Regulation, Neoplastic, Tumor progression, Neoplastic Stem Cells, Stem cell, Glioblastoma, Reprogramming, Neuroscience, Co-Repressor Proteins, Transcription Factors |
| الوصف: | 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 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, and 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, recapitulating the epigenetic landscape and phenotype of native TPCs. We reconstruct a network model that highlights critical interactions and identifies candidate therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in GBM, provides detailed insight into underlying gene regulatory programs, and suggests attendant therapeutic strategies. Howard Hughes Medical Institute Starr Cancer Consortium Burroughs Wellcome Fund Harvard Stem Cell Institute Klarman Family Foundation |
| وصف الملف: | application/pdf |
| تدمد: | 0092-8674 |
| DOI: | 10.1016/j.cell.2014.02.030 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::26e594f2b018953de6bcc0ed596a7861Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....26e594f2b018953de6bcc0ed596a7861 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00928674 |
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| DOI: | 10.1016/j.cell.2014.02.030 |