Genome-Wide CRISPR-Cas9 Screens Expose Genetic Vulnerabilities and Mechanisms of Temozolomide Sensitivity in Glioblastoma Stem Cells

Graham MacLeod, Danielle A. Bozek, Nishani Rajakulendran, Vernon Monteiro, Moloud Ahmadi, Zachary Steinhart, Michelle M. Kushida, Helen Yu, Fiona J. Coutinho, Florence M.G. Cavalli, Ian Restall, Xiaoguang Hao, Traver Hart, H. Artee Luchman, Samuel Weiss, Peter B. Dirks, Stephane Angers

Research output: Contribution to journalArticlepeer-review

121 Scopus citations

Abstract

MacLeod et al. describe genome-wide CRISPR-Cas9 screens identifying genetic vulnerabilities across a panel of patient-derived glioblastoma stem cell cultures. Regulators of stemness (SOX2, SOX9, DOT1L, and SOCS3) and stress response (ufmylation and ERAD pathways) govern the growth of glioblastoma stem cells. Chemogenomic screens using temozolomide identify modulators of sensitivity to chemotherapy.

Original languageEnglish (US)
Pages (from-to)971-986.e9
JournalCell Reports
Volume27
Issue number3
DOIs
StatePublished - Apr 16 2019

Keywords

  • CRISPR-Cas9
  • fitness genes
  • functional genomics
  • glioblastoma
  • glioblastoma stem cells

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

MD Anderson CCSG core facilities

  • Bioinformatics Shared Resource

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