Coopted temporal patterning governs cellular hierarchy, heterogeneity and metabolism in Drosophila neuroblast tumors
- Aix Marseille University, CNRS, France
- Université Côte d'Azur, CNRS, Inserm, France
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.
Data availability
Sequencing data have been deposited in GEO under accession codes GSE114986 and GSE114562.Codes generated for the numerical model are available at: http://dx.doi.org/10.17632/j2j9gmyb6m.1Codes used for single-cell RNA-seq analysis are available at: https://github.com/cedricmaurange/Genovese-et-al.-2019
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Single-cell RNA-seq analysis of Drosophila neuroblast tumorsNCBI Gene Expression Omnibus, GSE114986.
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RNA-binding proteins govern neural progenitor hierarchy during development and tumorigenesisNCBI Gene Expression Omnibus, GSE114562.
Article and author information
Author details
Cassandra Gaultier
Funding
Fondation ARC pour la Recherche sur le Cancer (PJA20141201621)
- Cédric Maurange
Fondation ARC pour la Recherche sur le Cancer
- Sara Genovese
Canceropôle PACA
- Cédric Maurange
Centre National de la Recherche Scientifique
- Cédric Maurange
Aix-Marseille Université
- Sara Genovese
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Cayetano Gonzalez, Institute for Research in Biomedicine, Spain
Version history
- Received: July 24, 2019
- Accepted: September 29, 2019
- Accepted Manuscript published: September 30, 2019 (version 1)
- Version of Record published: October 14, 2019 (version 2)
Copyright
© 2019, Genovese et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Coopted temporal patterning governs cellular hierarchy, heterogeneity and metabolism in Drosophila neuroblast tumors
eLife 8:e50375.
https://doi.org/10.7554/eLife.50375
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