A Single cell expression atlas of muscle and dermis during regeneration after wounding in Acomys cahirinus - an adult mammal model for de novo muscle regeneration

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Abstract: It is of major significance that we have discovered that during complete skin regeneration in the spiny mouse, Acomys, the skeletal muscle of the lower layers of the skin are regenerated despite the removal of all the connective tissue components of this tissue. This is in contrast to humans and the lab mouse, Mus, where the skin fibroses with a scar and no muscle is regenerated. The medical importance of this observation for both civilians and soldiers is profound because Acomys can also perfectly regenerate damage through the middle of a muscle belly. We propose here to take our recent microarray, qPCR and RNA-seq analysis of whole skin regeneration to the single cell level with single cell RNA-Seq (scRNA-seq) so that gene regulation patterns of the individual tissue components which make up the regenerating skin can be identified. This project will develop and utilize immunophenotyping panels and comprehensive single cell gene expression assays scRNA-Seq to resolve expression of individual cells and assess changes in tissue cell sub-populations across time between the Mus (scarring) and Acomys (regenerating). The outcome of this project is to identify the gene regulatory networks which characterize individual populations in a regenerating environment in contrast to a scarring environment, and to provide this as a resource to the regenerative medicine community. Future directions will be centered on functionally testing crucial genes for their ability to induce regeneration (hair follicles, sebaceous glands, skeletal muscle) in lieu of scarring with clear implications for its extrapolation to the human condition.