Poster Session 1 - B11
1,4+Neemat Mahmud, 1+Mekayla A. Storer, 1Scott A. Yuzwa, 1,2Michael J. Borrett, 1Dina Karamboulas, 1,2,3David R. Kaplan, 1,2,3,4Freda D. Miller
+ These authors contributes equally; 1 Program in Neurosciences and Mental Health, Hospital for Sick Children, Canada M5G 1L7; 2 Institute of Medical Sciences, University of Toronto; 3 Department of Molecular Genetics, University of Toronto; 4 Department of Physiology, University of Toronto, Toronto, Canada M5G 1A8
Regeneration of appendages is relatively common among invertebrates. In mammals, however, multi-tissue regeneration is largely restricted to the distal portion of the digit tip and involves the formation of a blastema. While the source of regenerative blastema cells in amphibians has been widely studied, the cellular origin and phenotypic identity of mammalian blastema cells are not well understood. Here, using an adult murine digit tip regeneration model we show that the blastema is predominantly comprised of mesenchymal precursor cells, and by utilizing several strains of transgenic mice including PdgfrαCreERT2 and Msx1CreERT2, we demonstrate that the blastema originates from pre-existing mesenchymal tissue. To characterize these mesenchymal blastema cells, we performed single cell RNA sequencing (scRNA-seq) over the course of digit tip regeneration. This analysis confirmed that the blastema is largely comprised of mesenchymal precursors with a relatively homogeneous transcriptional signature that is similar to that of the developing embryonic limb bud and other embryonic mesenchymal tissues. Together, these data support a model where, during successful adult digit tip regeneration, pre-existing mesenchymal precursor cells are recruited into the blastema, where they adopt an embryonic transcriptional identity, and ultimately recapitulate a limb development program to regenerate the digit.