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Updated: Jun 4, 2026
A Protocol for Rapid Post-mortem Cell Culture of Diffuse Intrinsic Pontine Glioma (DIPG)
Published on: March 7, 2017
Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma
Michelle Monje1, Siddhartha S Mitra, Morgan E Freret
1Department of Neurology, and Institute for Stem Cell Biology and Regenerative Medicine, Stanford University Medical Center, Stanford, CA 94305, USA. mmonje@stanford.edu
Abstract:
Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive tumors of childhood that are almost universally fatal. Our understanding of this devastating cancer is limited by a dearth of available tissue for study and by the lack of a faithful animal model. Intriguingly, DIPGs are restricted to the ventral pons and occur during a narrow window of middle childhood, suggesting dysregulation of a postnatal neurodevelopmental process. Here, we report the identification of a previously undescribed population of immunophenotypic neural precursor cells in the human and murine brainstem whose temporal and spatial distributions correlate closely with the incidence of DIPG and highlight a candidate cell of origin. Using early postmortem DIPG tumor tissue, we have established in vitro and xenograft models and find that the Hedgehog (Hh) signaling pathway implicated in many developmental and oncogenic processes is active in DIPG tumor cells. Modulation of Hh pathway activity has functional consequences for DIPG self-renewal capacity in neurosphere culture. The Hh pathway also appears to be active in normal ventral pontine precursor-like cells of the mouse, and unregulated pathway activity results in hypertrophy of the ventral pons. Together, these findings provide a foundation for understanding the cellular and molecular origins of DIPG, and suggest that the Hh pathway represents a potential therapeutic target in this devastating pediatric tumor.
Insights
Researchers identified a novel neural precursor cell in the brainstem linked to diffuse intrinsic pontine gliomas (DIPGs). The Hedgehog (Hh) signaling pathway is active in these pediatric brain tumors and may offer a therapeutic target.
Area of Science:
- Pediatric Oncology
- Developmental Neuroscience
- Cancer Biology
Background:
- Diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors with limited understanding and poor outcomes.
- Research is hindered by a lack of suitable models and tissue for studying DIPGs.
- DIPG occurrence in the ventral pons during childhood suggests a link to postnatal neurodevelopmental processes.
Purpose of the Study:
- To identify the cell of origin for diffuse intrinsic pontine gliomas.
- To investigate the role of developmental pathways in DIPG pathogenesis.
- To explore potential therapeutic targets for DIPG.
Main Methods:
- Identification and characterization of neural precursor cells in human and murine brainstems.
- Establishment of in vitro and xenograft models using early postmortem DIPG tissue.
- Analysis of Hedgehog (Hh) signaling pathway activity in DIPG cells and normal precursor cells.
Main Results:
- A novel population of immunophenotypic neural precursor cells was identified in the brainstem.
- The temporal and spatial distribution of these cells correlates with DIPG incidence.
- The Hedgehog (Hh) signaling pathway is active in DIPG cells and normal ventral pontine precursor-like cells, influencing DIPG self-renewal and causing pontine hypertrophy when dysregulated.
Conclusions:
- These findings identify a candidate cell of origin for DIPG and implicate dysregulated Hh pathway activity in its development.
- The Hedgehog (Hh) signaling pathway represents a potential therapeutic target for diffuse intrinsic pontine gliomas.
- This study provides a foundation for understanding the cellular and molecular origins of this devastating pediatric cancer.
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