Characterization of regeneration initiating cells during Xenopus laevis tail regeneration

Embryos are regeneration and wound healing masters. They not only rapidly close their wounds, remodel injured tissue without a scar, but also regenerate body parts. Many animal models with variable regenerative capabilities have already been studied. Additionally, with the introduction of high throughput techniques, novel regeneration mechanisms including genes and signaling pathways, and specialized cell types required for regeneration control in spatial and temporal aspects have been identified. Until now our knowledge has been limited to primarily the late phases of regeneration (> 1 day post injury). In this paper, we reveal the critical steps for regeneration initiation. We have discovered Regeneration Initiating Cells (RICs) using single cell and spatial transcriptomic analyses during tail regeneration in Xenopus laevis. RICs are formed transiently from the basal epidermal cells and are critical for the modification of the surrounding extracellular matrix to allow for migration of other cell types such as regeneration organizing cells that further promote regeneration. Absence or deregulation of RICs leads to excessive extracellular matrix deposition and regeneration defects.