A pontine-specific niche supports de novo gliomagenesis.

Authors

Adrija Pathak, Gregg B Wells, Vytas A Bankaitis, Zhigang Xie

Published in

Cell reports. Volume 45. Issue 8. Pages 117796. Aug 05, 2026. Epub Aug 05, 2026.

Abstract

Pediatric high-grade gliomas (HGGs) exhibit genetic profiles accompanied by anatomical specificities. These features suggest that specific anatomical niches favor the onset and/or progression of these diseases. However, such niche identities remain elusive as existing genetically engineered mouse models fail to recapitulate these anatomical specificities. Herein, we investigate the anatomical specificities of histone H3.1 lysine 27-to-methionine (H3.1K27M) and activating ACVR1 mutations for diffuse intrinsic pontine gliomas (DIPGs)-a major pons-specific pediatric HGG. We describe a murine model where expression of H3.1K27M and activating Acvr1 and Pik3ca mutations (which co-occur with H3.1K27M in human DIPGs) induces rapid gliomagenesis specifically in the pons. We show that gliomagenesis occurs predominantly at the trigeminal root entry zone (TREZ) and requires hyaluronan receptor (HMMR) signaling. Our data demonstrate that anatomical specificities of human HGGs can be accurately recapitulated in mice and identify the TREZ as an anatomical niche that plays a key role in DIPG pathogenesis.

PMID:
42555355
Bibliographic data and abstract were imported from PubMed on 06 Aug 2026.

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