A brain precursor atlas reveals the acquisition of developmental-like states in adult cerebral tumours

We map the development of mouse cerebrum across the developmental time-course, from embryonic day 12.5 to postnatal day 365, performing single-cell transcriptomics on >100,000 cells. By comparing this reference atlas to single-cell data from >100 glial tumours of the adult and pediatric human cerebrum, we find that tumour cells have an expression signature that overlaps with temporally restricted, embryonic radial glial precursors (RGPs) and their immediate sublineages. Further, we demonstrate that transformation of early RGPs in a genetic mouse model gives rise to adult cerebral tumours that show an embryonic/juvenile RGP identity. Together, these findings implicate the acquisition of embryonic-like states in the genesis of adult glioma, providing insight into the origins of human glioma, and identifying specific developmental cell types for therapeutic targeting. Overall design: 1) scRNA-seq of the mouse cerebrum from 11 developmental timepoints - mouse model: Sox2eGFP - # of GFP+ve samples: 11 samples - # of GFP-ve samples: 11 samples. 2) scRNA-seq of mouse cerebral tumours - mouse model: Nestin-Cre; P53 f/f; Pten f/+; R26 tdTomato/+ - # of samples: 2 samples.