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

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 () and Peter B. Dirks ()
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Akram A. Hamed: University of Toronto
Daniel J. Kunz: University of Cambridge
Ibrahim El-Hamamy: University of Toronto
Quang M. Trinh: Ontario Institute for Cancer Research
Omar D. Subedar: The Hospital for Sick Children
Laura M. Richards: University of Toronto
Warren Foltz: University Health Network
Garrett Bullivant: University of Toronto
Matthaeus Ware: University of Toronto
Maria C. Vladoiu: The Hospital for Sick Children
Jiao Zhang: The Hospital for Sick Children
Antony M. Raj: The Hospital for Sick Children
Trevor J. Pugh: Ontario Institute for Cancer Research
Michael D. Taylor: The Hospital for Sick Children
Sarah A. Teichmann: JJ Thomson Avenue
Lincoln D. Stein: University of Toronto
Benjamin D. Simons: JJ Thomson Avenue
Peter B. Dirks: University of Toronto

Nature Communications, 2022, vol. 13, issue 1, 1-15

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-31408-y

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