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Spatial transcriptomics reveals asymmetric cellular responses to injury in the regenerating spiny mouse (Acomys) ear

    • 1Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences), 3584CT Utrecht, The Netherlands;
    • 2Department of Biology/Chemistry, Osnabrück University, 49076 Osnabrück, Germany;
    • 3Wageningen University, Wageningen, 6708WE, The Netherlands;
    • 4University Medical Center Utrecht, 3584CX Utrecht, The Netherlands;
    • 5Department of Anatomy and Embryology, Leiden University Medical Center, and the Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden node, 2300RC Leiden, The Netherlands;
    • 6European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, 9713 AV Groningen, The Netherlands
Published September 19, 2023. https://doi.org/10.1101/gr.277538.122
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cover of Genome Research Vol 36 Issue 9
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Abstract

In contrast to other mammals, the spiny mouse (Acomys) regenerates skin and ear tissue, which includes hair follicles, glands, and cartilage, in a scar-free manner. Ear punch regeneration is asymmetric with only the proximal wound side participating in regeneration. Here, we show that cues originating from the proximal side are required for normal regeneration and use spatially resolved transcriptomics (tomo-seq) to understand the molecular and cellular events underlying this process. Analyzing gene expression across the ear and comparing expression modules between proximal and distal wound sides, we identify asymmetric gene expression patterns and pinpoint regenerative processes in space and time. Moreover, using a comparative approach with nonregenerative rodents (Mus, Meriones), we strengthen a hypothesis in which particularities in the injury-induced immune response may be one of the crucial determinants for why spiny mice regenerate whereas their relatives do not. Our data are available in SpinyMine, an easy-to-use and expandable web-based tool for exploring Acomys regeneration-associated gene expression.

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