Characterization of regeneration initiating cells during Xenopus laevis tail regeneration

Background: Embryos are regeneration and wound healing masters. They rapidly close wounds and scarlessly remodel and regenerate injured tissue. Regeneration has been extensively studied in many animal models using new tools such as single-cell analysis. However, until now, they have been based primarily on experiments assessing from 1 day post injury. Results: In this paper, we reveal that critical steps initiating regeneration occur within hours after injury. We discovered the regeneration initiating cells (RICs) using single-cell and spatial transcriptomics of the regenerating Xenopus laevis tail. RICs are formed transiently from the basal epidermal cells, and their expression signature suggests they are important for modifying the surrounding extracellular matrix thus regulating development. The absence or deregulation of RICs leads to excessive extracellular matrix deposition and defective regeneration. Conclusion: RICs represent a newly discovered transient cell state involved in the initiation of the regeneration process.