Régulation des cellules souches de la lignée germinale : La niche s’agrandit chez la drosophile

Abstract

L’intérêt médical des cellules souches provient de leur capacité à se diviser de manière asymétrique donnant naissance à une nouvelle cellule souche, et à une cellule capable de se différencier. Cette division est contrôlée à la fois par une identité spécifique des cellules souches et un microenvironnement complexe, appelé une niche, qui reste souvent inaccessible chez les mammifères. Au contraire, les outils génétiques disponibles chez la drosophile ont permis récemment d’identifier in vivo non seulement les cellules constituant la niche des cellules souches de la lignée germinale, mais également les signaux émis par celles-ci ainsi que les gènes cibles dans les cellules souches elles-mêmes. La conservation de ces mécanismes chez les mammifères, pour les cellules souches hématopoïétiques ou épithéliales, laisse envisager des applications thérapeutiques potentielles.

Our fascination for stem cells originates from their ability to divide asymmetrically in order to self-renew and produce daughter cells which can differentiate and replenish tissues. Stem cells could thus represent an unlimited source of differentiated cells that could be used to repair malformed, damaged or ageing tissues. Understanding how their behaviour is regulated is then of paramount medical interest. Specific microenvironments surrounding the stem cells, termed « niches », were proposed to play a major role in the balance between self-renewal and differentiation. However, it is only recently, in the case of the stem cells producing the germline (GSGs) in Drosophila, that the cells and signals creating a niche were identified for the first time. Here, we review how this niche has been defined at the cellular and functional levels in vivo, thanks to the powerful genetic tools available in Drosophila. Such studies have revealed adhesive interactions, cell-cycle modifications and intercellular signals that control the GSC behavior. Extracellular signals from the niche activate the BMP or JAK-STAT pathways in the GSCs and are necessary for their maintenance. Strickingly, both signaling pathways are also sufficient to convert differentiated germ cells into functional GSCs, demonstrating in vivo that a niche has the capacity to regenerate stem cells from differentiated cells. Rapid progresses have further identified direct links between these signaling pathways and the transcriptional regulation of the GSCs, providing a simple paradigm for stem cells regulation. Many of these features and signals are conserved in stem cells niches from Drosophila to mammals. We can thus hope that research on the GSCs in Drosophila will benefit therapeutic approaches to human degenerative diseases.