A glial blueprint for gliomagenesis


Gliomas are heterogeneous tumours derived from glial cells and remain the deadliest form of brain cancer. Although the glioma stem cell sits at the apex of the cellular hierarchy, how it produces the vast cellular constituency associated with frank glioma remains poorly defined. We explore glioma tumorigenesis through the lens of glial development, starting with the neurogenic–gliogenic switch and progressing through oligodendrocyte and astrocyte differentiation. Beginning with the factors that influence normal glial linage progression and diversity, a pattern emerges that has useful parallels in the development of glioma and may ultimately provide targetable pathways for much-needed new therapeutics.

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Fig. 1: Overview of glioma subtypes.
Fig. 2: The gliogenic switch and glioma.
Fig. 3: Glial developmental factors influence tumour identity.
Fig. 4: Astrocyte and oligodendrocyte lineage trajectories.


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The authors thank C. Gillespie for editing and reviewing this manuscript. This work was supported by grants from the US National Institutes of Health (NS071153 to B.D. and K01CA190235 and 5-T32HL092332-08 to S.M.G.) and the Cancer Prevention Research Institute of Texas (RP150334 and RP160192 to B.D.).

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Nature Reviews Neuroscience thanks B. Appel, W. Weiss, M. Monje and the other, anonymous reviewer(s) for their contribution to the peer review of this work.

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B.D. and D.L. researched data for the article and made a substantial contribution to the discussion of content and the writing, reviewing and editing of the manuscript before submission. S.M.G. researched data for the article.

Correspondence to Benjamin Deneen.

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Isocitrate dehydrogenase (IDH) status

Refers to whether a patient possesses a missense mutation in IDH1 or IDH2 that has been linked to glioma.

Frank glioma

A clinically diagnosed glioma.


A commonly used animal tumour model in which patient-derived cancer cells are transplanted under the skin or into the organ of interest in immune-deficient animals.

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Laug, D., Glasgow, S.M. & Deneen, B. A glial blueprint for gliomagenesis. Nat Rev Neurosci 19, 393–403 (2018). https://doi.org/10.1038/s41583-018-0014-3

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