Why mammals have poor regenerative ability has remained a long-standing question in biology. In regenerating vertebrates, injury can induce a process known as epimorphic regeneration to replace damaged structures. Using a 4-mm ear punch assay across multiple mammalian species, here we show that several Acomys spp. (spiny mice) and Oryctolagus cuniculus completely regenerate tissue, whereas other rodents including MRL/MpJ ‘healer’ mice heal similar injuries by scarring. We demonstrate ear-hole closure is independent of ear size, and closure rate can be modelled with a cubic function. Cellular and genetic analyses reveal that injury induces blastema formation in Acomys cahirinus. Despite cell cycle re-entry in Mus musculus and A. cahirinus, efficient cell cycle progression and proliferation only occurs in spiny mice. Together, our data unite blastema-mediated regeneration in spiny mice with regeneration in other vertebrates such as salamanders, newts and zebrafish, where all healthy adults regenerate in response to injury.

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Published in Nature Communications, v. 7, article no. 11164, p. 1-16.

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Funding for this work was provided by the National Science Foundation (NSF) and the Office for International Science and Engineering (OISE) to A.W.S. (IOS-1353713) and V.O.E. (IOS-1353857). Additional funding was provided to A.W.S. by the University of Kentucky.

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Sequencing data have been deposited in the NCBI database under accession code GSE71761.

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Supplementary Information: Supplementary Figures 1-9 and Supplementary Tables 1-5

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Supplementary Information: Peer Review file

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Supplementary Data 1