Periosteal response to bone fracture at single nuclei resolution

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.23.546220v1?rss=1 Authors: Perrin, S., Wotawa, C.-A., Luka, M., Coulpier, F., Masson, C., Menager, M., Colnot, C. Abstract: Bone regeneration is a highly efficient process allowing bones to fully regenerate after fracture. Skeletal stem/progenitor cells (SSPCs) allowing bone regeneration are recruited from several sources, including the periosteum located at the outer surface of bones. Periosteal SSPCs are major actors of bone healing and display the unique property to form both bone and cartilage after fracture. Yet, the steps of periosteal SSPCs activation and differentiation leading to osteogenesis and chondrogenesis remain poorly understood. Here, we generated a single-nuclei atlas of the periosteum at steady-state and in response to bone fracture. We described the heterogeneity of the uninjured periosteum and identified a population of periosteal SSPCs expressing stemness markers, such as Pi16 and Ly6a (Sca1). After fracture, we observed major changes in cell populations with a reduction of the SSPC population, a concomitant increase in injury-induced fibrogenic cells and immune cells, followed by the appearance of chondrocytes and osteoblasts. We show that periosteal SPPCs respond to injury via a unique differentiation trajectory. Cells first leave their stem/progenitor state to adopt an injury-activated fibrogenic fate, prior to undergoing either osteogenesis or chondrogenesis. Overall, our study provides a complete temporal topography of the fracture healing environment and the dynamic response of periosteal SSPC to injury, redefining our knowledge on the early steps of bone regeneration. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC