The skin dermis evolves from a multipotent pool of fibroblasts, which differentiate into distinct subpopulations creating the different dermal layers and respective architecture. This dermal maturation process is governed by a tight balance of fibroblast proliferation, quiescence and extracellular matrix (ECM) deposition. During wound healing, quiescent fibroblasts restart proliferating, migrate into the wound bed and deposit ECM to regenerate the skin. Which signalling networks control the switch in fibroblast behaviour and how the fibroblast subpopulations organize themselves and influence each other during dermal maturation and wound healing is currently unknown. Deregulations of these complex developmental processes in the dermis are associated with several skin pathologies including fibrosis or chronic wounds. To understand the regulators of the dermal fibroblast state switch, we integrated several single cell RNA-seq datasets of whole skin, covering all major developmental timepoints during embryonic and postnatal growth. Our novel integrated single cell RNA-seq dataset is able to recapitulate key skin developmental changes observed in vivo. Comprehensive bioinformatic analysis of the dermal fibroblast populations reveal distinct set of growth and transcription factors controlling the developmental fibroblast state switch in the skin. These involve members of the AP-1, IGF and TGFβ signalling pathways which are regulated by a combination of epigenetic, transcriptional, cytoskeletal and metabolic mechanisms that we are currently investigating in skin explant cultures and advanced 2D/3D cell culture models. In summary, we elucidate the dynamic behaviour of fibroblast subpopulations and the underlying signalling networks balancing proliferation and ECM production during dermal development in homeostasis and wound healing which will pave the way to new therapeutic targets enhancing skin regeneration. Our novel integrated whole skin dataset represents a valuable resource for studying fibroblasts and other cell types in skin development.

ESDR591 - Exploring the molecular basis for the dermal fibroblast state switch

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.