Hedgehog-responsive candidate cell of origin for diffuse intrinsic pontine glioma

摘要: Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive tumors of childhood that almost universally fatal. Our understanding this devastating cancer is limited by a dearth available tissue for study and the lack faithful animal model. Intriguingly, DIPGs restricted to ventral pons occur during narrow window middle childhood, suggesting dysregulation postnatal neurodevelopmental process. Here, we report identification previously undescribed population immunophenotypic neural precursor cells in human murine brainstem whose temporal spatial distributions correlate closely with incidence DIPG highlight candidate cell origin. Using early postmortem tumor tissue, have established vitro xenograft models find Hedgehog (Hh) signaling pathway implicated many developmental oncogenic processes active cells. Modulation Hh activity has functional consequences self-renewal capacity neurosphere culture. The also appears be normal precursor-like mouse, unregulated results hypertrophy pons. Together, these findings provide foundation cellular molecular origins DIPG, suggest represents potential therapeutic target pediatric tumor.