“Re-generating the principles of appendage regeneration in the single-cell era”
Can Aztekin, Ph.D.
Group Leader at Swiss Federal Institute of Technology Lausanne (EPFL)
Can Aztekin received his BSc in Biological Sciences and Bioengineering from Sabanci University, Turkey in 2014. He then carried out his MSc in Biomedical Engineering at Koc University, Turkey in 2016 under the supervision of Assoc Prof Tamer Onder. Afterwards, he obtained his PhD in Developmental Biology from the University of Cambridge, UK and worked with Prof John Gurdon at the Gurdon Institute, UK (2021). In 2021, he joined the Swiss Federal Institute of Technology Lausanne (EPFL), Switzerland, as an ELISIR Scholar and established his independent research group.
Unlike mammals, Xenopus laevis tadpoles have a high regenerative potential for their appendages, such as their limbs and tails. Moreover, tadpoles exhibit naturally occurring regeneration-competent and-incompetent developmental stages allowing comparative studies to reveal principles of regeneration that can be harnessed for regenerative medicine purposes. However, regeneration has been poorly characterized at the cellular level, and cellular principles guiding different appendage regeneration scenarios remain elusive.
To reveal a comprehensive cellular landscape of regeneration, we first performed single-cell RNA-seq (scRNA-Seq) to intact tails and following tail amputations in regeneration-competent and -incompetent stage tadpoles (Aztekin et al., Science, 2019). By comparing the transcriptome of single cells, we identified a previously uncharacterized population which we named 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 promote stem and progenitor cell proliferation, ROCs act as a signaling center orchestrating regeneration. ROCs relocalization ability depends on the myeloid lineage activity that is also required for setting a regeneration-permissive environment (Aztekin et al., Development, 2020). Afterwards, by using scRNA-Seq, we characterized cell types mediating limb development and regeneration (Aztekin et al. bioRxiv, 2020). We found that tadpole limb regeneration does not use ROCs, but re-deploy limb development associated apical-ectodermal-ridge (AER) cells to act as a signaling center for regeneration. Upon amputations, limb regeneration-competent tadpoles can specify AER cells at their amputation plane, whilst -incompetent tadpoles cannot. By establishing regenerating ex vivo limb cultures, we uncovered that cartilage/bone growth (chondrogenesis) associated secreted factors block AER cell formation and regeneration potential in limb regeneration-incompetent tadpoles. Collectively, these results suggest that appendage regeneration is context-dependent at the cellular level, and characterization of signaling center populations mediating appendage regeneration offers new perspectives for mammalian limb regeneration possibilities.
Date-Time: Wednesday, October 13, 2021 at 15:30
Host: Doç. Dr. Işık Yuluğ
All interested are cordially invited