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Ecdysone and Mediator trigger a metabolic switch uncoupling cell cycle from cell growth to end proliferation in Drosophila neural stem cells

ABSTRACT: Stem cells are highly abundant and proliferate rapidly during early development but become a rare population in most adult organs. The molecular mechanisms causing stem cells to exit proliferation at a specific time are not well understood. Here, we show that changes in energy metabolism induced by the steroid hormone Ecdysone initiate an irreversible cascade of events leading to cell cycle exit in Drosophila neural stem cells. We show that the timely induction of oxidative phosphorylation and the mitochondrial respiratory chain are required in neuroblasts to uncouple cell cycle progression from cell growth. This results in a progressive reduction in neuroblast cell size and ultimately in terminal differentiation. Neuroblasts isolated from brain tumors fail to undergo this shrinkage process and this may explain why they are immortalized. Our findings show that cell size control can be modified by systemic hormonal signaling and reveal a unique connection between metabolism and proliferation control in stem cells.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE53265 | GEO | 2014/08/14

SECONDARY ACCESSION(S): PRJNA231473

REPOSITORIES: GEO

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Ecdysone and Mediator trigger a metabolic switch uncoupling cell cycle from cell growth to end proliferation in Drosophila neural stem cells

Project description:Stem cells are highly abundant and proliferate rapidly during early development but become a rare population in most adult organs. The molecular mechanisms causing stem cells to exit proliferation at a specific time are not well understood. Here, we show that changes in energy metabolism induced by the steroid hormone Ecdysone initiate an irreversible cascade of events leading to cell cycle exit in Drosophila neural stem cells. We show that the timely induction of oxidative phosphorylation and the mitochondrial respiratory chain are required in neuroblasts to uncouple cell cycle progression from cell growth. This results in a progressive reduction in neuroblast cell size and ultimately in terminal differentiation. Neuroblasts isolated from brain tumors fail to undergo this shrinkage process and this may explain why they are immortalized. Our findings show that cell size control can be modified by systemic hormonal signaling and reveal a unique connection between metabolism and proliferation control in stem cells. Comparison of transcriptomes of Drosophila melanogaster central brain NBs from wild-type larval NBs, wild type pupal NBs and med27 RNAi pupal NBs.

2014-08-14 | E-GEOD-53265 | biostudies-arrayexpress

Imp/IGF2BP levels modulate individual neural stem cell growth and division through myc mRNA stability

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Project description:Drosophila neuroblasts have emerged as a model for stem cell biology that is ideal for genetic analysis but is limited by the lack of cell-type specific gene expression data. Here, we describe a methodology to isolate large numbers of pure neuroblasts and differentiating neurons that retain both cell cycle and lineage characteristics. We determine transcriptional profiles by mRNA sequencing and identify 28 predicted neuroblast specific transcription factors, which can be arranged in a network containing hubs for Notch signaling, growth control and chromatin regulation. Overexpression and RNAi for these factors identify Klumpfuss as a regulator of self-renewal. We show that loss of Klu function causes premature differentiation while overexpression results in the formation of transplantable brain tumors. Our data represent a valuable resource for Drosophila developmental neurobiology and we describes methodology that can be applied to other invertebrate stem cell lineages as well. comparison of transcriptomes of Drosophila melanogaster larval neuroblasts and their differentiated daughter cells (neurons)

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Myc and the Tip60 chromatin remodeling complex control neuroblast maintenance and polarity in Drosophila

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Genome wide profiling of Su(H) [CSL] binding in Drosophila melanogaster larval CNSs where Notch is hyperactive in neuroblasts for 24 hours

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