Coopted temporal patterning governs cellular hierarchy, heterogeneity and metabolism in Drosophila neuroblast tumors

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

The following data sets were generated

Article and author information

Author details

  1. Sara Genovese

    Institut de Biologie du Développement de Marseille, Aix Marseille University, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Raphaël Clément

    Institut de Biologie du Développement de Marseille, Aix Marseille University, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Cassandra Gaultier

    Institut de Biologie du Développement de Marseille, Aix Marseille University, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6401-9163
  4. Florence Besse

    Institut de Biologie Valrose, Université Côte d'Azur, CNRS, Inserm, Nice, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4672-1068
  5. Karine Narbonne-Reveau

    Institut de Biologie du Développement de Marseille, Aix Marseille University, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Fabrice Daian

    Institut de Biologie du Développement de Marseille, Aix Marseille University, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Sophie Foppolo

    Institut de Biologie du Développement de Marseille, Aix Marseille University, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Nuno Miguel Luis

    Institut de Biologie du Développement de Marseille, Aix Marseille University, CNRS, Marseille, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5438-9638
  9. Cédric Maurange

    Institut de Biologie du Développement de Marseille, Aix Marseille University, CNRS, Marseille, France
    For correspondence
    cedric.maurange@univ-amu.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8931-1419

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

  1. Cayetano Gonzalez, Institute for Research in Biomedicine, Spain

Version history

  1. Received: July 24, 2019
  2. Accepted: September 29, 2019
  3. Accepted Manuscript published: September 30, 2019 (version 1)
  4. 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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  1. Sara Genovese
  2. Raphaël Clément
  3. Cassandra Gaultier
  4. Florence Besse
  5. Karine Narbonne-Reveau
  6. Fabrice Daian
  7. Sophie Foppolo
  8. Nuno Miguel Luis
  9. Cédric Maurange
(2019)
Coopted temporal patterning governs cellular hierarchy, heterogeneity and metabolism in Drosophila neuroblast tumors
eLife 8:e50375.
https://doi.org/10.7554/eLife.50375

Share this article

https://doi.org/10.7554/eLife.50375

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