Transcriptional signature of Drosophila wing disc regeneration
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ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE17408 | GEO | 2010/10/22
SECONDARY ACCESSION(S): PRJNA118861
REPOSITORIES: GEO
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Project description:Research on the ability of certain organisms to reconstruct missing structures of their bodies is still in its infancy, despite numerous efforts performed in multiple species. Using expression profile analyses on different timepoints that cover wound healing and regeneration processes (0, 24 and 72 hours post injury), we studied the regenerative behaviour of fragmented wing imaginal discs of D. melanogaster implanted into adult flies. First, through the comparison between cut and intact discs, we identified the effect of implantation on the regeneration process. Filtering this information, we then constructed the specific early regeneration gene signature of wing discs in which multiple transcription factors, immune response genes and members of the JNK, Notch and WNT signaling pathways seem to play an important role. We next compared the transcriptomes of discs 24 and 72 hours after fragmentation to characterize the regenerative machinery and observed a temporal decrease in the cellular metabolic processes, RNA processing and gene expression machinery, suggesting the discs normal activity was stopped on this first interval of time in response to injury and implantation offences. Based on the expression patterns, we elaborated a catalogue of genes involved in wing disc regeneration divided into four classes (wound healing, regeneration, quick response, constant response). Imaginal discs from third instar larvae were 3/4 fragmented, implanted into the abdomen of adult flies and cultured. In order to subtract the noise due to implantation, we repeated the same protocol using intact discs that were cultivated for 24h. Therefore, a total of 12 microarrays were hybridized: four microarrays (with total RNA from non cut wing discs at 0 and 24 hours) were used to assess the effect of the implantation procedure in intact wing discs and the rest (8) were used to measure changes in gene expression in the first 24 hours after disc dissection and implantation (total RNA from wing discs at 0 and 24 hours was hybridized) and during the period between 24 and 72 hours after the cut (total RNA from wing discs at 24 and 72 hours was hybridized). At least two independent total RNA extractions were carried out (using the RNeasy Protect Mini Kit from Qiagen Inc.) for each condition. The four microarrays hybridized for each pair of conditions were done in biological replicate pairs with dyes swapped to take dye bias into account. The whole set of microarrays was normalized following the same protocol, extracting in each case the list of significant genes (at least 1.5-fold change, FDR adjusted pvalue < 0.05).
2010-10-22 | E-GEOD-17408 | biostudies-arrayexpress
Project description:Regeneration of fragmented Drosophila imaginal discs occurs in an epimorphic manner, involving local cell proliferation at the wound site. Following disc fragmentation, cells at the wound site activate a restoration program through wound healing, regenerative cell proliferation and repatterning of the tissue. However, the interplay of signaling cascades, driving these early reprogramming steps, is not well understood. Here we profiled the transcriptome of regenerating cells in the early phase within twenty-four hours after wounding. We found that JAK/STAT signaling becomes activated at the wound site and promotes regenerative cell proliferation in cooperation with Wingless (Wg) signaling. In addition, we demonstrated that the expression of Drosophila insulin-like peptide 8 (dilp8), which encodes a paracrine peptide to delay the onset of pupariation, is controlled by JAK/STAT signaling in early regenerating discs. Our findings suggest that JAK/STAT signaling plays a pivotal role in coordinating regenerative disc growth with organismal developmental timing. In order to analyze transcriptome change in early regenerating imaginal disc, Drosophila prothorasic leg discs were fragmented (to anterior one-quarter or posterior three-quarters) and cultured ex vivo in adult fly abdomen. Regenerating cells in early regeneration phase (at 12 or 24 hours after wounding) were subjected to transcriptome profiling with Affymetrix microarrays. For control samples, the corresponding regions of uncut-cultured discs and uncut-uncultured discs were used.
2015-04-10 | E-GEOD-54868 | biostudies-arrayexpress
Project description:Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the main events participating in the healing of a wound, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila imaginal discs, do not model all aspects of the repair process, but allow exploring many unanswered features of the healing response; e.g., which are the signal(s) responsible for initiating tissue remodeling? How is the sealing of the epithelia achieved? Or which are the inhibitory cues that cancel the healing machinery upon completion? Answering these and other questions demands in first place the identification and functional analysis of wound-specific genes. A variety of different microarray analyses of murine and humans have identified characteristic profiles of gene expression at the wound site, however, very few functional studies in healing regulation have been carried out. We developed an experimentally controlled method to culture imaginal discs that allows live imaging and biochemical analysis and is healing-permissive. Employing this approach, we performed a comparative genome-wide profiling between those Drosophila imaginal cells actively involved in healing versus their non-engaged siblings. This lets us identify a set of potential wound-specific genes. Importantly, besides identifying and categorizing new genes, we functionally tested many of their gene products by genetic interference and overexpression in a healing assay. This non-saturated analysis defines a relevant set of new genes whose changes in expression levels are functionally significant for proper tissue repair. There is promise that our newly identified wound-healing genes will guide future work in the more complex mammalian wound response. We developed a healing-permissive in vitro culture system for fly imaginal discs: we used one-channel microarrays for comparing healing-engaged cells (showing activation of the JNK signaling cascade) to cells not participating in healing (silent JNK activity) in wounded wing imaginal discs in culture. Employing this method, we aimed detecting the relevant genes involved in disc healing through microarray analysis. We compared cells actively involved in healing to those not involved and identified a whole set of upregulated or downregulated genes. They were annotated, clustered by expression profiles, chromosomal locations and presumptive functions. Most importantly, we functionally tested them genetically in a healing assay.
2015-04-13 | E-GEOD-62863 | biostudies-arrayexpress
Project description:The systemic response to injury in Drosophila melanogaster is characterized by the activation of specific signaling pathways that facilitate the regeneration of wounded tissue and help coordinate wound healing with organism growth. The mechanisms by which damaged tissues influence the development and function of peripheral non-injured tissues is not fully understood. Injury was induced in early third instar larvae via temperature-dependent cell death in wing imaginal discs. Microarray analysis using RNA isolated from injured and control was used to identify genes underlying the systemic injury response. We identified 150 genes which were differentially expressed in response to localized cell death in wing imaginal discs. Upregulated genes were associated biological processes including carnitine biosynthesis, signal transduction and regulation of oxidoreductase activity while terms associated with downregulated genes included wound healing, imaginal disc-derived wing hair outgrowth, and regulation of glutamatergic synaptic transmission. Pathway analysis revealed that wing disc damage led to changes in fatty acid, cysteine, and carnitine metabolism. One gene, 14-3-3ζ, which encodes a known regulator of Ras/MAPK signaling was identified as a potential regulator of transdetermination during tissue regeneration. Our results raise the possibility that immune function and cell proliferation during wing disc repair and regeneration in Drosophila may require the sulfur amino acid cysteine and its’ metabolites, taurine and glutathione, similar to what has been reported during tissue repair in mammals. Further, it seems likely that imaginal disc damage stimulates the mobilization of fatty acids to support the energetically demanding process of tissue regeneration. The roles of additional genes that are differentially regulated following imaginal disc injury remain to be elucidated.
2017-09-30 | GSE94938 | GEO
Project description:Regeneration of fragmented Drosophila imaginal discs occurs in an epimorphic manner, involving local cell proliferation at the wound site. Following disc fragmentation, cells at the wound site activate a restoration program through wound healing, regenerative cell proliferation and repatterning of the tissue. However, the interplay of signaling cascades, driving these early reprogramming steps, is not well understood. Here we profiled the transcriptome of regenerating cells in the early phase within twenty-four hours after wounding. We found that JAK/STAT signaling becomes activated at the wound site and promotes regenerative cell proliferation in cooperation with Wingless (Wg) signaling. In addition, we demonstrated that the expression of Drosophila insulin-like peptide 8 (dilp8), which encodes a paracrine peptide to delay the onset of pupariation, is controlled by JAK/STAT signaling in early regenerating discs. Our findings suggest that JAK/STAT signaling plays a pivotal role in coordinating regenerative disc growth with organismal developmental timing.
2015-04-10 | GSE54868 | GEO
Project description:Identifying the genetic program that induces limb regeneration in salamanders is an important resource for regenerative medicine, which currently lacks tools to promote regeneration of functional body structures. The genetic network underlying limb regeneration has been elusive due to the complexity of the injury response that occurs concomitant to blastema formation. Here we performed parallel expression profile time courses of non-regenerative lateral wounds versus amputated limbs in axolotl. We show that limb regeneration occurs in three distinguishable phases--early wound healing followed by a transition phase leading to establishment of the limb development program. By focusing on the transition phase, we identified 93 strictly regeneration-associated genes involved in oxidative stress response, chromatin modification, epithelial development and limb development. The specific expression of the genes was confirmed by in situ hybridization. Regeneration-specific expression databases are critical resources for understanding how regeneration-relevant phenotypes can be induced from adult cells Regeneration of the axolotl forelimb lower arm was compared with the healing of a deep lateral injury in a high density timecourse (uncut, 3h, 6h, 9h, 12h, 24h, 36h, 52h, 72h, 120h, 168h, 288h and 528h after injury). Three independent biological replicates were performed using separate cluches of animals. Amputated and lateral wound samples were made as matched contralateral samples of four pooled animals per timepoint.
2013-01-01 | E-GEOD-36451 | biostudies-arrayexpress
Project description:While considerable progress has been made towards understanding the complex processes and pathways that regulate human wound healing, regenerative medicine has been unable to develop therapies that coax the natural wound environment to heal scar-free. The inability to induce perfect skin regeneration stems partly from our limited understanding of how scar-free healing occurs in a natural setting. Here we have investigated the wound repair process in adult axolotls and demonstrate that they are capable of perfectly repairing full thickness excisional wounds made on the flank. In the context of mammalian wound repair, our findings reveal a substantial reduction in hemostasis, reduced neutrophil infiltration and a relatively long delay in production of new extracellular matrix (ECM) during scar-free healing. Additionally, we test the hypothesis that metamorphosis leads to scarring and instead show that terrestrial axolotls also heal scar-free, albeit at a slower rate. Analysis of newly forming dermal ECM suggests that low levels of fibronectin and high levels of tenascin-C promote regeneration in lieu of scarring. Lastly, a genetic analysis during wound healing comparing epidermis between aquatic and terrestrial axolotls suggests that matrix metalloproteinases may regulate the fibrotic response. Our findings outline a blueprint to understand the cellular and molecular mechanisms coordinating scar-free healing that will be useful towards elucidating new regenerative therapies targeting fibrosis and wound repair. We used microarray analysis to determine the gene expression changes that take place during scar free wound healing in aquatic and terrestrial axolotl salamanders. Epidermal tissue was harvested using a 4mm biopsy punch. Two wounds were made along the flank and posterior to the forelimbs. Harvested epidermis was pooled for each animal. Four biological replicates were collected from uninjured epidermis (D0) and at 1, 3, and 7 days post injury.
2012-01-31 | E-GEOD-35255 | biostudies-arrayexpress
Project description:Wound healing is an essential homeostatic mechanism that maintains the epithelial barrier integrity after tissue damage. Although we know the main events participating in the healing of a wound, many of the underlying molecular mechanisms remain unclear. Genetically amenable systems, such as wound healing in Drosophila imaginal discs, do not model all aspects of the repair process, but allow exploring many unanswered features of the healing response; e.g., which are the signal(s) responsible for initiating tissue remodeling? How is the sealing of the epithelia achieved? Or which are the inhibitory cues that cancel the healing machinery upon completion? Answering these and other questions demands in first place the identification and functional analysis of wound-specific genes. A variety of different microarray analyses of murine and humans have identified characteristic profiles of gene expression at the wound site, however, very few functional studies in healing regulation have been carried out. We developed an experimentally controlled method to culture imaginal discs that allows live imaging and biochemical analysis and is healing-permissive. Employing this approach, we performed a comparative genome-wide profiling between those Drosophila imaginal cells actively involved in healing versus their non-engaged siblings. This lets us identify a set of potential wound-specific genes. Importantly, besides identifying and categorizing new genes, we functionally tested many of their gene products by genetic interference and overexpression in a healing assay. This non-saturated analysis defines a relevant set of new genes whose changes in expression levels are functionally significant for proper tissue repair. There is promise that our newly identified wound-healing genes will guide future work in the more complex mammalian wound response.
2015-04-13 | GSE62863 | GEO
Project description:Mammalian skin wounds heal by forming fibrotic scars. We report that reindeer antler velvet exhibits regenerative wound healing, whereas identical injury to back skin forms scar. This regenerative capacity was retained following ectopic transplantation of velvet to scar-forming sites. Single-cell mRNA/ATAC-Sequencing revealed that while uninjured velvet fibroblasts resembled human fetal fibroblasts, back skin fibroblasts were enriched in pro-inflammatory features resembling adult human fibroblasts. Injury elicited site-specific immune polarization; back skin fibroblasts amplified the immune response, whereas velvet fibroblasts adopted an immunosuppressive state leading to restrained myeloid maturation and hastened immune resolution ultimately enabling myofibroblast reversion to a regeneration-competent state. Finally, regeneration was blunted following application of back skin associated immunostimulatory signals or inhibition of pro-regenerative factors secreted exclusive to velvet fibroblasts. This study highlights a unique model to interrogate mechanisms underlying divergent healing outcomes and nominates both decoupling of stromal-immune crosstalk and reinforcement of pro-regenerative fibroblast programs to mitigate scar.
2023-02-23 | PXD035749 | Pride
Project description:We report the changes in chromatin accessibility associated with regeneration in wing imaginal discs at two developmental timepoints during L3. Wing discs were ablated using tissue-specific expression of the pro-apoptotic gene eiger at an early timepoint (day 7) when the discs retain high regenerative capacity and at a late time point (day 9) when regenerative capacity has significantly declined. ATAC-seq was performed on these discs after 40 hr of ablation and compared to identically staged unablated discs. We detect 14,142 open chromatin peaks after merging overlapping peaks from 3 biological repeats of all 4 conditions. Of these, 349 change significantly (log2fc>0.5, p<0.1) either opening or closing upon damage in early L3 discs, while only 55 open or close in late L3 discs. We describe two consequential groups of peak changes, those that are damage responsive (DR) in early L3 (222 peaks) and those that are maturity silenced (MS), open in early damaged L3 and closed in late damaged L3 (729 peaks). 28 peaks fall in the overlap of these two groups.
2020-06-11 | GSE140755 | GEO