Tumour-derived gliogenesis sustains dedifferentiation-dependent tumour growth in theDrosophilaCNS

Abstract Fate-restricted cells can acquire stem cell-like properties through dedifferentiation, enabling them to gain the plasticity required for differentiation into multiple lineages. Tumour plasticity is prominently observed in brain cancers, where transient cell state changes are linked to resistance to conventional therapies. In this study, we demonstrate that a sub-population of dedifferentiated tumour neural stem cells (NSCs) in Drosophila, induced by the knockdown of prospero (pros), can generate its own glial niche. Temporal patterning, known to influence oncogenic competence and tumour malignancy, plays a key role in this process. Specifically, we show that de novo gliogenesis occurs in the more differentiated Syncrip+ (Syp+) NSC population. Modulating Syp levels alters the size of the glial niche, subsequently affecting tumour size. Furthermore, the tumour-associated glial niche expands through cell division and fails to cease proliferation on time due to dysregulated ecdysone signalling, contributing to niche expansion. Our findings reveal that tumours arising via dedifferentiation establish their own supportive glial microenvironment, which sustains tumour growth. Competing Interest Statement The authors have declared no competing interest.