Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells.

Détails

ID Serval
serval:BIB_FD67C2344F6A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells.
Périodique
Cell
Auteur(s)
Suvà M.L., Rheinbay E., Gillespie S.M., Patel A.P., Wakimoto H., Rabkin S.D., Riggi N., Chi A.S., Cahill D.P., Nahed B.V., Curry W.T., Martuza R.L., Rivera M.N., Rossetti N., Kasif S., Beik S., Kadri S., Tirosh I., Wortman I., Shalek A.K., Rozenblatt-Rosen O., Regev A., Louis D.N., Bernstein B.E.
ISSN
1097-4172 (Electronic)
ISSN-L
0092-8674
Statut éditorial
Publié
Date de publication
24/04/2014
Peer-reviewed
Oui
Volume
157
Numéro
3
Pages
580-594
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
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. PAPERCLIP:
Mots-clé
Basic Helix-Loop-Helix Transcription Factors/metabolism, Brain Neoplasms/genetics, Brain Neoplasms/metabolism, Brain Neoplasms/pathology, Cell Differentiation, Cell Line, Tumor, Cells, Cultured, Co-Repressor Proteins/metabolism, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Glioblastoma/genetics, Glioblastoma/metabolism, Glioblastoma/pathology, Humans, Neoplastic Stem Cells/metabolism, Neoplastic Stem Cells/pathology, Nerve Tissue Proteins/metabolism, Oligodendrocyte Transcription Factor 2, Regulatory Elements, Transcriptional, Transcription Factors/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/07/2018 9:39
Dernière modification de la notice
20/08/2019 16:28
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