RRC ID 57689
Author Genovese S, Clément R, Gaultier C, Besse F, Narbonne-Reveau K, Daian F, Foppolo S, Luis NM, Maurange C.
Title Coopted temporal patterning governs cellular hierarchy, heterogeneity and metabolism in Drosophila neuroblast tumors.
Journal Elife
Abstract 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.
Volume 8
Published 2019-9-30
DOI 10.7554/eLife.50375
PII 50375
PMID 31566561
PMC PMC6791719
MeSH Animals Asymmetric Cell Division / genetics* Body Patterning / genetics* Cell Differentiation / genetics Cell Proliferation / genetics* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development Gene Expression Regulation, Developmental Humans Larva / genetics* Larva / growth & development Neural Stem Cells / metabolism Neural Stem Cells / pathology Neurons / metabolism
IF 7.08
Times Cited 0