Fig. 1

GBM organoids mimic the pathologic transition zones and molecular heterogeneity of GBM patient tumors. A H&E staining of GBM 3D organoids (right panel) reveals histological zones comparable to GBM primary patient tumors (left panel). The perivascular region and hypoxic core in primary patient tumors (left panel) are mimicked by the organoid proliferative rim and hypoxic core regions (right panel), respectively. B To compare the molecular signature of these histological regions, the organoids were stained whole to label the entire outer rim region, and single cells were isolated. C Limiting-dilution assays showed that the organoid proliferative rim is functionally enriched for stem cells compared to the hypoxic core. Calculated stem cell frequencies and 95% confidence intervals are shown. D Upon RNA-seq analysis of single cells, distinct cell-type signatures were found to be enriched within spatially separate niches in the organoids. E Mapping expression in organoids to the regional Ivy GAP database showed region-specific enrichment. Scale bar = 100 µm