Outer Radial Glia-Like Cancer Stem Cells Contribute to Heterogeneity of Glioblastoma
Glioblastoma is a devastating form of brain cancer. To identify aspects of tumor heterogeneity that may illuminate drivers of tumor invasion, we created a glioblastoma tumor cell atlas with single-cell transcriptomics of cancer cells mapped onto a reference framework of the developing and adult human brain. We find that multiple GSC subtypes exist within a single tumor. Within these GSCs, we identify an invasive cell population similar to outer radial glia (oRG), a fetal cell type that expands the stem cell niche in normal human cortex. Using live time-lapse imaging of primary resected tumors, we discover that tumor derived oRG-like cells undergo characteristic mitotic somal translocation behavior previously only observed in human development, suggesting a reactivation of developmental programs. In addition, we show that PTPRZ1 mediates both mitotic somal translocation and glioblastoma tumor invasion. These data suggest that the presence of heterogeneous GSCs may underlie glioblastoma’s rapid progression and invasion. Supplemental Table Legends Supplemental Table 1 (Related to Figure 1). Clinical Annotations and Sequencing Information Clinical annotations of tumor samples as available, including age, sex, diagnosis and karyotypic/mutational information. Sequencing parameters for each sample, including the number of cells, average reads per cell, average genes per cell and method of single-cell capture. Supplemental Table 2 (Related to Figure 1). Cluster Markers Cluster markers and cluster cell type interpretations for each dataset based upon clustering analysis. Supplemental Table 3 (Related to Figure 1 and 3) Exome Sequencing Results Exome sequencing results from 5 tumors. Supplemental Table 4 (Related to Figure 1, 2, 3) Cell Metadata Table of metadata by cell, including cell id, tumor sample, and cell type. Supplemental Table 5 (Related to Figures 5 and 6). Transplantation Single-cell Identification Cluster identity summary for mouse and organoid single-cell experiments. Supplemental Table 6 (Related to Figure 5). PTPRZ1 Knockdown Differentiation Gene Expression Differential gene expression summary with the small hairpin mediated knockdown of PTPRZ1 in primary cortical and primary glioblastoma samples.