Principles of Xenopus appendage regeneration

Seminar from Dr. Can Aztekin, Department from University of Cambridge
Affiliation: The Welcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge
 
Abstract:
 
Can Aztekin Principles of Xenopus appendage regeneration Unlike mammals, Xenopus tadpoles have a high regenerative potential for their appendages such as tails and limb buds. Furthermore, having naturally occurring regeneration-competent and-incompetent stages allows comparative studies to reveal principles of regeneration that can be harnessed for regenerative medicine purposes. However, regeneration has been poorly characterized at the single-cell level, and cell types and transcriptome changes accompanying regeneration remains largely elusive. To address this, we first performed scRNA-seq to intact tails and in a time course following tail amputation in regeneration-competent and -incompetent stage tadpoles (Aztekin C. et al., Science, 2019). By comparing the transcriptome of single cells, we identified a previously uncharacterized population which we termed as regeneration-organizing-cells (ROCs). ROCs are present in intact tails and specifically relocalize to the amputation plane of regeneration-competent tadpoles and form the specialized wound epidermis. Elimination of ROCs blocks regeneration, and grafting tissues that contain ROCs enable ectopic outgrowths. By secreting a cocktail of ligands that can enable progenitor cell proliferation, ROCs act as a signal centre that mediates regeneration. ROCs relocalization ability depends on the myeloid lineage activity. Upon tail amputation, regeneration-incompetent tadpoles fail to suppress amputation induced inflammation. Meanwhile, suppression of inflammation enables decreased apoptosis levels which then enables remodelling of the extracellular matrix, and finally ROCs to relocalize to the amputation plane. As a next step, we ask whether tail and limb regeneration utilize similar mechanisms and ROCs based regeneration model is also seen in Xenopus limb regeneration. Collectively, identification of a single cell type, ROCs, that can orchestrate regeneration and characterize the specialized wound epidermis offers new perspectives to regenerative medicine.