Drosophila melanogaster
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA231473 | ENA |
REPOSITORIES: ENA
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Project description:Steroid hormones control various cellular activities in a context-dependent manner. For example, ecdysone, which acts through a type II nuclear receptor, has seemingly opposite effects in Drosophila wing precursors, promoting proliferation during larval stages, and triggering proliferation arrest at pupariation. We find that wing precursors proliferate normally in the complete absence of the ecdysone receptor (EcR), whether ecdysone is present or not, suggesting that ecdysone overrides a default anti-proliferative activity of the receptor. By contrast, termination of proliferation by high concentration of 20E at the end of larval life requires ligand-induced transcriptional activation by the receptor. The switch from one mode of regulation to the other is determined by ligand level, as measured with a calibrated EcR transcriptional reporter and ex vivo proliferation assays. Accordingly, RNA Seq analysis uncovers distinct transcriptional responses to different doses of ecdysone. Some genes are only activated at high doses (high threshold targets) and likely to comprise genes that stop proliferation at pupariation, when ecdysone titres are high. We find that other target genes respond to all physiological concentrations of ecdysone. Some of these genes are known to promote proliferation and could therefore contribute to the pro-proliferation activity of low-level ecdysone. Finally, we show mathematically and with synthetic reporters that relatively simple combinations of regulatory elements can recapitulate the behaviour of both types of target genes.
2023-08-24 | GSE236166 | GEO
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
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.
2014-08-14 | GSE53265 | GEO
Project description:Pulsed ecdysone signaling remodels cell cycle dynamics, causing distinct primary and secondary cell cycle arrests, similar to those observed in the wing during metamorphosis.
2017-02-10 | GSE77562 | GEO
Project description:Steroid hormones act as important developmental switches and their nuclear receptors regulate many genes. However, few hormone-dependent enhancers have been characterized and important aspects of their sequence architecture, cell type-specific activating and repressing functions, or the regulatory roles of their chromatin structure have remained unclear. We used STARR-seq, a recently developed enhancer-screening assay, and ecdysone signaling in two different Drosophila cell types to derive the first genome-wide hormone-dependent enhancer activity maps. We demonstrate that enhancer activation depends on cis-regulatory motif combinations that differ between cell types and can predict cell type-specific ecdysone targeting. Activated enhancers are often not accessible prior to induction. Enhancer repression following hormone treatment is independent of receptor motifs and receptor binding to the enhancer as we show using ChIP-seq, but appears to rely on motifs for other factors, including Eip74. Our strategy is applicable to study signal-dependent enhancers for different pathways and across organisms. STARR-seq was performed in S2 and OSC cells treated with ecdysone in two replicates. DHS-seq before and after treatment was done with single-end sequencing in two replicates. RNA-seq (with and without ecdysone) was performed with a strand-specific protocol using single-end sequencing in two replicates in S2. ChIP-seq (with and without ecdysone) was performed single-end sequencing in two replicates in S2 cells.
2014-03-27 | E-GEOD-47691 | biostudies-arrayexpress
Project description:Great progress has been made in identifying transcriptional programs that establish stem cell identity. In contrast, we have limited insight into how these programs are down-graded in a timely manner to halt proliferation and allow for cellular differentiation. Drosophila embryonic neuroblasts undergo such a temporal progression, initially dividing to bud off daughters that divide once (type I), then switching to generating non-dividing daughters (type 0), and finally exiting the cell cycle. We identify six early transcription factors that drive neuroblast and type I daughter proliferation. Early factors are gradually replaced by three late factors, acting to trigger the type I->0 daughter proliferation switch and eventually to stop neuroblasts. Early and late factors regulate each other and four key cell cycle genes, providing a logical genetic pathway for these transitions. The identification of this extensive driver-stopper temporal program controlling neuroblast lineage progression may have implications for studies in many other systems.
2018-03-08 | GSE103660 | GEO
Project description:In contrast to stage-specific transcription factors, the role of ubiquitous transcription factors in neuronal development remains a matter of scrutiny. Here, we demonstrated that a ubiquitous factor NF-Y is essential for neural progenitor maintenance during brain morphogenesis. Deletion of the NF-YA subunit in neural progenitors by using nestin-cre transgene in mice resulted in significant abnormalities in brain morphology, including a thinner cerebral cortex and loss of striatum during embryogenesis. Detailed analyses revealed a progressive decline in multiple neural progenitors in the cerebral cortex and ganglionic eminences, accompanied by induced apoptotic cell death and reduced cell proliferation. In neural progenitors, the NF-YA short isoform lacking exon 3 is dominant and co-expressed with cell cycle genes. ChIP-seq analysis from the cortex during early corticogenesis revealed preferential binding of NF-Y to the cell cycle genes, some of which were confirmed to be downregulated following NF-YA deletion. Notably, the NF-YA short isoform disappears and is replaced by its long isoform during neuronal differentiation. Forced expression of the NF-YA long isoform in neural progenitors resulted in a significant decline in neuronal count, possibly due to the suppression of cell proliferation. Collectively, we elucidated a critical role of the NF-YA short isoform in maintaining neural progenitors, possibly by regulating cell proliferation and apoptosis. Moreover, we identified an isoform switch in NF-YA within the neuronal lineage in vivo, which may explain the stage-specific role of NF-Y during neuronal development.
2024-01-11 | GSE244758 | GEO
Project description:The proneural NEUROG2 is essential for neuronal commitment, cell cycle exit and neuronal differentiation. Characterizing genes networks regulated downstream of NEUROG2 is therefore of prime importance. To identify NEUROG2 early response genes, we combined gain of function in the neural tube with a global detection of modified transcripts using microarrays. We included in our study a mutant form of NEUROG2 (NEUROG2AQ) that cannot bind DNA and cannot trigger neurogenesis. Using this approach, we identified 942 genes modified at the onset of NEUROG2 activation. The global analysis of functions regulated by NEUROG2 allowed unmasking its rapid impact on cell cycle control. We found that NEUROG2 specifically represses a subset of cyclins acting at the G1 and S phases of the cell cycle, thereby impeding S phase re-entry. This repression occurs before modification of p27kip1, indicating that the decision to leave the cell cycle precedes the activation of this Cyclin-dependant Kinase Inhibitor. Moreover, NEUROG2 down-regulates only one of the D-type cyclins, cyclinD1, and maintaining cyclinD1 blocks the ability of the proneural to trigger cell cycle exit, without altering its capacity to trigger neuronal differentiation. The fact that NEUROG2 represses a subset but not all cell cycle regulators indicates that cell cycle exit is not an indirect consequence of neuronal differentiation but is precisely controlled by NEUROG2. Altogether our findings indicate that NEUROG2, by specifically repressing G1 and S cyclins, allows committed neuronal precursors to perform their last mitosis but blocks their re-entry in the cell cycle, thus favouring cell cycle exit. Stage HH10-11 embryos (11 to 15 somites) were electroporated with a control vector (pGIG-GFP), a NEUROG2-expressing vector (pCIGNEUROG2-GFP), or a NEUROG2AQ-expressing vector (pCIGNEUROG2AQ-GFP). For each biological replicate, neural tubes from 20 embryos were pooled for GFP+ cells collection. GFP+ cells were collected 6h later using FACS sorting (Epics Altra HSS cell sorter, Toulouse Rio platform) and processed for RNA probe preparation and hybridization on Affymetrix microarrays. For each experimental condition, four biological replicates were processed.
2012-05-04 | E-GEOD-37782 | biostudies-arrayexpress
Project description:Emergency myelopoiesis (EM) is critical for immune defense against pathogens, which requires rapid replenishing of mature myeloid cells. The EM process involves a rapid cell cycle switch from the quiescent hematopoietic stem cells (HSCs) to highly proliferative myeloid progenitors (MPs). How this cell cycle switch is regulated remains poorly understood. Here, we reveal that ATG7, a critical autophagy factor is essential for the rapid proliferation of MPs during human myelopoiesis. Peripheral blood (PB) mobilized HSPCs with ATG7 knock-down or HSPCs derived from ATG7-/- human embryonic stem cells (hESCs) exhibit severe defect in proliferation at MP stage during myeloid/granulocytes differentiation. ATG7 deficient MPs show substantially elevated P53 protein and up-regulation of P53 signaling pathway genes. Mechanistically, ATG7 dependent autophagy mediates P53 degradation in lysosome that allows normal proliferation of MPs. Together, we reveal an essential role of autophagy for P53 degradation in cell cycle switch during human myelopoiesis
2023-01-25 | GSE223219 | GEO
Project description:mSWI/SNF or BAF chromatin regulatory complexes are dosage-sensitive regulators of human neural development frequently mutated in autism and intellectual disability. Cell cycle exit and differentiation of neural stem/progenitor cells is accompanied by BAF subunit switching to generate neuron-specific nBAF complexes. We manipulated the timing of BAF subunit exchange in vivo and found that early loss of the npBAF subunit BAF53a stalls cell cycle exit to disrupt neurogenesis. Loss of BAF53a results in decreased chromatin accessibility at specific neural transcription factor binding sites, including the pioneer factors Sox2 and Ascl1, due to Polycomb accumulation. This results in repression of cell cycle genes, thereby blocking cell cycle progression and differentiation. Cell cycle block upon Baf53a deletion could be rescued by premature expression of the nBAF subunit BAF53b but not by other major drivers of proliferation or differentiation. Wnt, EGF, FGF, Sox2, myc or Pax6 all fail to maintain proliferation in the absence of BAF53a, highlighting a novel mechanism underlying neural progenitor cell cycle exit in the continued presence of extrinsic proliferative cues.
2021-01-18 | GSE164990 | GEO