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

Publication ,  Journal Article
Suvà, ML; Rheinbay, E; Gillespie, SM; Patel, AP; Wakimoto, H; Rabkin, SD; Riggi, N; Chi, AS; Cahill, DP; Nahed, BV; Curry, WT; Martuza, RL ...
Published in: Cell
April 24, 2014

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:

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Published In

Cell

DOI

EISSN

1097-4172

Publication Date

April 24, 2014

Volume

157

Issue

3

Start / End Page

580 / 594

Location

United States

Related Subject Headings

  • Transcription Factors
  • Regulatory Elements, Transcriptional
  • Oligodendrocyte Transcription Factor 2
  • Nerve Tissue Proteins
  • Neoplastic Stem Cells
  • Humans
  • Glioblastoma
  • Gene Expression Regulation, Neoplastic
  • Epigenesis, Genetic
  • Developmental Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Suvà, M. L., Rheinbay, E., Gillespie, S. M., Patel, A. P., Wakimoto, H., Rabkin, S. D., … Bernstein, B. E. (2014). Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell, 157(3), 580–594. https://doi.org/10.1016/j.cell.2014.02.030
Suvà, Mario L., Esther Rheinbay, Shawn M. Gillespie, Anoop P. Patel, Hiroaki Wakimoto, Samuel D. Rabkin, Nicolo Riggi, et al. “Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells.Cell 157, no. 3 (April 24, 2014): 580–94. https://doi.org/10.1016/j.cell.2014.02.030.
Suvà ML, Rheinbay E, Gillespie SM, Patel AP, Wakimoto H, Rabkin SD, et al. Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell. 2014 Apr 24;157(3):580–94.
Suvà, Mario L., et al. “Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells.Cell, vol. 157, no. 3, Apr. 2014, pp. 580–94. Pubmed, doi:10.1016/j.cell.2014.02.030.
Suvà ML, Rheinbay E, Gillespie SM, Patel AP, Wakimoto H, Rabkin SD, Riggi N, Chi AS, Cahill DP, Nahed BV, Curry WT, Martuza RL, Rivera MN, Rossetti N, Kasif S, Beik S, Kadri S, Tirosh I, Wortman I, Shalek AK, Rozenblatt-Rosen O, Regev A, Louis DN, Bernstein BE. Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells. Cell. 2014 Apr 24;157(3):580–594.
Journal cover image

Published In

Cell

DOI

EISSN

1097-4172

Publication Date

April 24, 2014

Volume

157

Issue

3

Start / End Page

580 / 594

Location

United States

Related Subject Headings

  • Transcription Factors
  • Regulatory Elements, Transcriptional
  • Oligodendrocyte Transcription Factor 2
  • Nerve Tissue Proteins
  • Neoplastic Stem Cells
  • Humans
  • Glioblastoma
  • Gene Expression Regulation, Neoplastic
  • Epigenesis, Genetic
  • Developmental Biology