Coopted temporal patterning governs cellular hierarchy, heterogeneity and metabolism in Drosophila neuroblast tumors.
Elife. 2019 Sep 30;8. pii: e50375. doi: 10.7554/eLife.50375.
Genovese S1, Clément R#1, Gaultier C#1, Besse F2, Narbonne-Reveau K1, Daian F1, Foppolo S1, Luis NM1, Maurange C1.
1. Aix Marseille Univ, CNRS, IBDM, Equipe Labellisée LIGUE Contre le Cancer, Marseille, France.
2. Université Côte d’Azur, CNRS, Inserm, Institut de Biologie Valrose, Nice, France.
# Contributed equally
It is still unclear what drives progression of childhood tumors. During Drosophila larval development, asymmetrically-dividing neural stem cells, called neuroblasts, progress through an intrinsic temporal patterning program that ensures cessation of divisions before adulthood. We previously showed that temporal patterning also delineates an early developmental window during which neuroblasts are susceptible to tumor initiation (Narbonne-Reveau et al., 2016). Using single-cell transcriptomics, clonal analysis and numerical modeling, we now identify a network of twenty larval temporal patterning genes that are redeployed within neuroblast tumors to trigger a robust hierarchical division scheme that perpetuates growth while inducing predictable cell heterogeneity. Along the hierarchy, temporal patterning genes define a differentiation trajectory that regulates glucose metabolism genes to determine the proliferative properties of tumor cells. Thus, partial redeployment of the temporal patterning program encoded in the cell of origin may govern the hierarchy, heterogeneity and growth properties of neural tumors with a developmental origin.