Drosophila melanogaster
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ABSTRACT:
PROVIDER: PRJNA126497 | ENA |
REPOSITORIES: ENA
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Project description:Cell competition promotes the elimination of weaker cells from a growing population. Here we investigate how cells of Drosophila wing imaginal discs distinguish “winners” from “losers” during cell competition. Using genomic and functional assays we have identified Maxwell`s Demon (Mwd), a cell membrane protein conserved in multicellular animals. Our results suggest that the membrane protein Mwd is a dedicated component of the cell competition response that is required and sufficient to label cells as “winners” or “losers”. In Drosophila, the mwd locus produces three isoforms, mwdubi, mwdLose-A and mwdLose-B. Basal levels of mwdubi are constantly produced. During competition the mwdLose isoforms are upregulated in prospective loser cells. Cell-cell comparison of relative mwdLose and mwdubi levels ultimately determine which cell undergoes apoptosis. This “extracellular code” may constitute an ancient mechanism to terminate competitive conflicts among cells. Two samples have been analysed: tub>dmyc>Gal4 transgene cells (competitor) and tub>cd2>Gal4 control cells (non competitor) at different time points (0, 12, 24 and 48 hours). Each experiment was replicated 6 times, three of them by dye swap.
2011-02-09 | E-GEOD-21230 | biostudies-arrayexpress
Project description:Cell competition promotes the elimination of weaker cells from a growing population. Here we investigate how cells of Drosophila wing imaginal discs distinguish “winners” from “losers” during cell competition. Using genomic and functional assays we have identified Maxwell`s Demon (Mwd), a cell membrane protein conserved in multicellular animals. Our results suggest that the membrane protein Mwd is a dedicated component of the cell competition response that is required and sufficient to label cells as “winners” or “losers”. In Drosophila, the mwd locus produces three isoforms, mwdubi, mwdLose-A and mwdLose-B. Basal levels of mwdubi are constantly produced. During competition the mwdLose isoforms are upregulated in prospective loser cells. Cell-cell comparison of relative mwdLose and mwdubi levels ultimately determine which cell undergoes apoptosis. This “extracellular code” may constitute an ancient mechanism to terminate competitive conflicts among cells.
2011-02-09 | GSE21230 | GEO
Project description:WDR5 is a highly-conserved nuclear protein that performs multiple scaffolding functions in the context of chromatin. WDR5 is also a promising target for pharmacological inhibition in cancer, with small molecule inhibitors of an arginine-binding pocket of WDR5 (the "WIN" site) showing efficacy against a range of cancer cell lines in vitro. Efforts to understand WDR5, or establish the mechanism of action of WIN site inhibitors, however, are stymied by its many functions in the nucleus, and a lack of knowledge of the conserved gene networks—if any—that are under its control. Here, we have performed comparative genomic analyses to identify the conserved sites of WDR5 binding to chromatin, and the conserved genes regulated by WDR5, across a diverse panel of cancer cell lines. We show that a specific cohort of protein synthesis genes (PSGs) are invariantly bound by WDR5, demonstrate that the WIN site anchors WDR5 to chromatin at these sites, and establish that PSGs are both acute and persistent targets of WIN site blockade. Together, these data reveal that WDR5 plays a predominant transcriptional role in biomass accumulation and reinforce the notion that WIN site inhibitors kill sensitive cancer cells by disrupting protein synthesis homeostasis.
2020-01-17 | GSE136451 | GEO
Project description:WIN Site inhibitors bind the WIN Site of WDR5 resulting in decreased transcription of WDR5 target genes, many of which encode components of the protein synthesis machinery. In this study, we determined proteome alterations in an MLL-rearranged leukemia cell line treated for either 24 or 72 hours with a WIN Site inhibitor. The data from these studies, along with Ribo-Seq, RNA-Seq, and CRISPR screen experiments, guided us in assembling a collection of compounds that, when combined with WIN Site inhibitor, synergistically inhibit growth of MLL-rearranged leukemia cells.
2023-07-04 | PXD035129 | Pride
Project description:Cell competition is a new notion of old theory Darwinian theory in cell level. It is notorious as its function on cancer promotion, actually, cell competition is a critical checkpoint machinery in development, its proper operation roles out suboptimal cells and makes sure the high quality of basic materials make up organism. Although its function has been revealed on other organs, it remains mysterious in brain development. In this paper, we get a compromised cell competitional model by knocking out endothelial Brd4, the lack of Brd4 in endothelial cell induces less neural stem cells deaths and compromised cell competition, endothelial Brd4 regulates cell competition is Testican2 dependent, Testican2 can deposit Sparc. We find a noncanonical role of the canonical negative cell competitional regulator Sparc in the fate decision of neural stem cells, neural stem cells highly expressing Sparc steps forward differentiation. We also find a compromised cell competition in AD patients, by cloning a point mutant of Brd4 found in a group of AD, we reveals that the mutant lose the potential of cell competition promotion. We put forward a new strategy for the treatment of aging related diseases by enhancing cell competitional state.
2023-01-25 | GSE223131 | GEO
Project description:Dietary transgenerational effects on sperm competition
| PRJNA360276 | ENA
Project description:Cell competition is a fundamental surveillance mechanism that preserves epithelial integrity by eliminating aberrant “loser” cells through interactions with surrounding “winner” cells. However, how winner cells sense and eliminate transformed neighbours remains poorly understood. Here, using a synNotch-based transcriptomic screen, we identify a mechanosensor–mechanotransducer axis linking the actin crosslinker filamin to the ETV4/5–PRKG2 pathway that mediates extrusion of oncogenically transformed cells through cell competition. Within an epithelial monolayer, transformed cells increase their volume, inducing membrane stretching. In adjacent normal cells, filamin senses the increased membrane tension and triggers activation of ETV4/5. Activated ETV4/5 then upregulate PRKG2, which promotes volume expansion of normal cells, consequently pushing back and driving the extrusion of transformed cells. These findings reveal that dynamic changes in cell volume can trigger mechanotransduction-driven cell competition, uncovering a fundamental pathway by which epithelial tissues maintain homeostasis and defend against oncogenic transformation.
2026-04-20 | GSE309822 | GEO
Project description:Cell competition was originally described in Drosophila as a process for selection of the fittest cells. Using genetic mosaic mouse models and bone marrow chimeras, we have characterized a form of cell competition that selects for the least damaged cells. This competition is controlled by p53 but is distinct from the classical p53-mediated DNA damage response: it persists for months, is specific to the hematopoietic stem and progenitor cells, and depends on the relative rather than absolute level of p53 in competing cells. The competition appears to be mediated by a non-cell autonomous induction of growth arrest and senescence-related gene expression in outcompeted cells with higher p53 activity. p53-mediated cell competition of this type could potentially contribute to the clonal expansion of incipient cancer cells. This microarray experiment is aimed at identification of candidate genes that mediate this competition. It compares mRNA expression patterns of HSCs with different levels of p53 activity in either competitive or non-competitive conditions (isolated from either wild type, mutant p53, or mosaic wt/mutant p53 mice (R26-mp53mice) after irradiation).
2010-04-01 | GSE20912 | GEO