OLIG2 mediates a rare targetable stem cell fate transition in sonic hedgehog medulloblastoma.

ABSTRACT: Functional cellular heterogeneity in tumours often underlies incomplete response to therapy and relapse. Previously, we demonstrated that the growth of the paediatric brain malignancy, sonic hedgehog subgroup medulloblastoma, is rooted in a dysregulated developmental hierarchy, the apex of which is defined by characteristically quiescent SOX2⁺ stem-like cells. Integrating gene expression and chromatin accessibility patterns in distinct cellular compartments, we identify the transcription factor Olig2 as regulating the stem cell fate transition from quiescence to activation, driving the generation of downstream neoplastic progenitors. Inactivation of Olig2 blocks stem cell activation and tumour output. Targeting this rare OLIG2-driven proliferative programme with a small molecule

SUBMITTER: Desai K 

PROVIDER: S-EPMC11794873 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature