Studying the Cell-Lineage Accountable for Scarless Skin Regeneration

• Applicant: Yuval Rinkevich, Ph.D.
• Subject Area: Developmental Biology ; Dermatology
• Term: from 2016 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 315284225

Why are scars created? Skin wounds in adult mammals are repaired by scar tissue, a fibrotic extracellular matrix that neither resembles (morphologically) nor performs (physiologically) as the normal tissue, and that impede organ function. In contrast to the formation of scars in adult mammals, the fetal back skin regenerates a complete replica of the original tissue following injury, without scarring. Endowed with such latent abilities, why is it that the adult mammalian skin responds to injury by scarring instead of complete regeneration? This enigmatic query carries evolutionary as well as future clinical considerations. Adopting a cellular genealogy view of scarring, we have identified an embryonic fibroblast lineage (En1-lineage positive fibroblasts; EPFs) that is the primary contributor to all fibrotic scar developments in the back skin. This proposal aims to understand the key fetal/adult transition in response to skin injuries, namely, from scarless regeneration to skin fibrosis, through a detailed cell-lineage analysis of EPFs cellular and molecular characteristics. Our specific objectives are: (i) to characterize the scarless-to-scar phenotypic transition, at single cell and lineage levels in vivo (ii) to determine lineage-specific molecular changes during the scarless-to-scar phenotypic transition (iii) to assess the functions of candidate genes in alleviating scar development. Our ultimate goal is to develop a knowledge basis for therapeutic strategies to ameliorate fibrotic programs from ensuing.

• DFG Programme: Research Grants