The multilayered transcriptional architecture of glioblastoma ecosystems

In isocitrate dehydrogenase wildtype glioblastoma (GBM), cellular heterogeneity across and within tumors may drive therapeutic resistance. Here we analyzed 121 primary and recurrent GBM samples from 59 patients using single-nucleus RNA sequencing and bulk tumor DNA sequencing to characterize GBM transcriptional heterogeneity. First, GBMs can be classified by their broad cellular composition, encompassing malignant and nonmalignant cell types. Second, in each cell type we describe the diversity of cellular states and their pathway activation, particularly an expanded set of malignant cell states, including glial progenitor cell-like, neuronal-like and cilia-like. Third, the remaining variation between GBMs…

• CC
  Conquer Cancer Foundation
• AS
  American Society of Clinical Oncology
• FN
  Fonds National de la Recherche Luxembourg
• CF
  Council for Higher Education
• S
  Servier
• NI
  National Institutes of Health

  Awards: P30CA240139, P30CA006516, R21NS114873, P30CA013696, R21CA256575, R01CA237208, P30CA034196, P50CA165962
• UO
  University of Texas MD Anderson Cancer Center
• JS
  Japan Society for the Promotion of Science

  Award: P30CA013696
• NC
  National Cancer Institute

  Awards: R01CA239721, R01CA276765, P30CA034196, P50CA165962, P30CA240139, P30CA006516, P30CA013696