Reconstructing and Reprogramming the Tumor-Propagating Potential of Glioblastoma Stem-like Cells | Zendy

Mario L. Suvà | Zendy; Esther Rheinbay | Zendy; Shawn Gillespie | Zendy; Anoop P. Patel | Zendy; Hiroaki Wakimoto | Zendy; Samuel D. Rabkin | Zendy; Nicolò Riggi | Zendy; S. Andrew | Zendy; Daniel P. Cahill | Zendy; Brian V. Nahed | Zendy; William T. Curry | Zendy; Robert L. Martuza | Zendy; Miguel N. Rivera | Zendy; Nikki E. Rossetti | Zendy; Simon Kasif | Zendy; Samantha Beik | Zendy; Sabah Kadri | Zendy; Itay Tirosh | Zendy; Ivo Wortman | Zendy; Alex K. Shalek | Zendy; Orit Rozenblatt–Rosen | Zendy; Aviv Regev | Zendy; David N. Louis | Zendy; B Bernstein | Zendy

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Reconstructing and Reprogramming the Tumor-Propagating Potential of Glioblastoma Stem-like Cells

Author(s) -

Mario L. Suvà,

Esther Rheinbay,

Shawn Gillespie,

Anoop P. Patel,

Hiroaki Wakimoto,

Samuel D. Rabkin,

Nicolò Riggi,

S. Andrew,

Daniel P. Cahill,

Brian V. Nahed,

William T. Curry,

Robert L. Martuza,

Miguel N. Rivera,

Nikki E. Rossetti,

Simon Kasif,

Samantha Beik,

Sabah Kadri,

Itay Tirosh,

Ivo Wortman,

Alex K. Shalek,

Orit Rozenblatt–Rosen,

Aviv Regev,

David N. Louis,

B Bernstein

Publication year - 2014

Publication title -

cell

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 26.304

H-Index - 776

eISSN - 1097-4172

pISSN - 0092-8674

DOI - 10.1016/j.cell.2014.02.030

Subject(s) - biology , reprogramming , glioblastoma , stem cell , cancer research , microbiology and biotechnology , genetics , cell

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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