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.
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•Glioblastoma tumors have heterogenous cell and cancer stem cell composition•Glioblastomas re-activate a developmental cell type, outer radial glia•These outer radial glia undergo mitotic somal translocation mediated by PTPRZ1•Outer radial glia in glioblastoma promote tumor invasion through PTPRZ1
Kriegstein and colleagues use single-cell RNA sequencing to create a tumor atlas of primary glioblastoma tumors. One interesting population they identify is the outer radial glia-like cell, a cell type found during normal cortical development that undergoes a characteristic mitotic somal translocation “jump-and-divide.” In tumors, these cells may promote invasive behavior.
Cortical neurons exhibit extreme diversity in gene expression as well as in morphological and electrophysiological properties
. Most existing neural taxonomies are based on either transcriptomic
or ...morpho-electric
criteria, as it has been technically challenging to study both aspects of neuronal diversity in the same set of cells
. Here we used Patch-seq
to combine patch-clamp recording, biocytin staining, and single-cell RNA sequencing of more than 1,300 neurons in adult mouse primary motor cortex, providing a morpho-electric annotation of almost all transcriptomically defined neural cell types. We found that, although broad families of transcriptomic types (those expressing Vip, Pvalb, Sst and so on) had distinct and essentially non-overlapping morpho-electric phenotypes, individual transcriptomic types within the same family were not well separated in the morpho-electric space. Instead, there was a continuum of variability in morphology and electrophysiology, with neighbouring transcriptomic cell types showing similar morpho-electric features, often without clear boundaries between them. Our results suggest that neuronal types in the neocortex do not always form discrete entities. Instead, neurons form a hierarchy that consists of distinct non-overlapping branches at the level of families, but can form continuous and correlated transcriptomic and morpho-electrical landscapes within families.
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