Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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RNA-Seq of wounds comparing gene expression in wild type and Alox15 deficient mice during day 0, day 4 and day 7 post-wounding.

ABSTRACT: Alox15 is a gene which encodes 12/15-LOX, an enzyme that generates bioactive lipid mediators. This experiment is designed to look at the impact of genetic deletion of Alox15 in punch wounds in skin, in order to determine how the protein may be involved in regulating wound healing. Punch wounds were generated on skin of wild type (C57BL/6) and Alox15 deficient mice, which were then allowed to heal for up to 7 days. Samples were obtained at varying time points for RNASeq analysis. Group sizes were 4 for each strain and at each time point. Following processing, one wild type (WT-d0-br3) sample failed a quality control check (Alox15 gene expression data indicated it was a knockout sample) and was removed from further analysis. Users may wish to remove this sample before re-using the dataset.

INSTRUMENT(S): Illumina HiSeq 4000

ORGANISM(S): Mus musculus

SUBMITTER: Valerie O'Donnell

PROVIDER: E-MTAB-12845 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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.

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RNA-Seq of wounds comparing gene expression in wild type and Alox15 deficient mice during day 0, day 4 and day 7 post-wounding.

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