A Brain Precursor Atlas Reveals the Acquisition of Developmental-like States in Adult Cerebral Tumours

Overview

Journal Nat Commun

Specialty Biology

Date 2022 Jul 19

PMID 35853870

Authors

Akram A Hamed

Daniel J Kunz

Ibrahim El-Hamamy

Quang M Trinh

Omar D Subedar

Laura M Richards

Warren Foltz

Garrett Bullivant

Matthaeus Ware

Maria C Vladoiu

Jiao Zhang

Antony M Raj

Trevor J Pugh

Michael D Taylor

Sarah A Teichmann

Lincoln D Stein

Benjamin D Simons

Peter B Dirks

Affiliations

Soon will be listed here.

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.

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