Repository logo
 

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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Abstract

Human cerebral cancers are known to contain cell types resembling the varying stages of neural development. However, the basis of this association remains unclear. Here, 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 paediatric 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 prenatal transformation of 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.

Description

Keywords

Animals, Brain, Cerebrum, Child, Glioma, Humans, Mice, Neurogenesis, Telencephalon

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

13

Publisher

Springer Science and Business Media LLC
Sponsorship
Wellcome Trust (098357/Z/12/Z)
Royal Society (RP/R1/180165)
Wellcome Trust (203828/Z/16/Z)
Medical Research Council (MC_PC_17230)