Integrative spatial analysis reveals a multi-layered organization of glioblastoma

Glioma contains malignant cells in diverse states. Here, we combine spatial transcriptomics, spatial proteomics, and computational approaches to define glioma cellular states and uncover their organization. We find three prominent modes of organization. First, gliomas are composed of small local environments, each typically enriched with one major cellular state. Second, specific pairs of states preferentially reside in proximity across multiple scales. This pairing of states is consistent across tumors. Third, these pairwise interactions collectively define a global architecture composed of five layers. Hypoxia appears to drive the layers, as it is associated with a long-range organization that includes all…

• IC
  Israel Cancer Research Fund
• BI
  Broad Institute
• EC
  European Commission
• DF
  Deutsche Forschungsgemeinschaft
• WI
  Weizmann Institute of Science
• CF
  Council for Higher Education
• NI
  National Institutes of Health
• DO
  Division of Chemistry