Group Leader French Institute of Health and Medical Research (Inserm) French Institute of Health and Medical Research (Inserm), Nord-Pas-de-Calais, France
Abstract: Adult muscle stem cells (MuSCs) allow the regeneration of skeletal muscle. They represent a potential therapeutic interest to treat trauma and muscular disorders. It is therefore essential to better understand the mechanisms that govern MuSCs engraftment, activation and self-renewal in order to design new strategies and enhance the potential of MuSCs. In this context, the role of the biological clock is poorly understood, whereas the regeneration of many tissues, such as the skin or the intestine, has been shown to be coordinated by the circadian clock. Our hypothesis is that the biological clock controls the regenerative capacity of skeletal muscle by gating MuSCs function to the right time window, leading an optimal response at the time of day when the risk of injury is greatest. Our results show a circadian remodeling of the MuSCs proteome associated with rhythmic changes in MuSCs metabolism and behavior during the circadian cycle. Through an innovative approach combining original mouse models, proteomics, and human MuSCs analysis, we identified the molecular targets of the biological clock in MuSCs. We showed that the MuSCs clock controls their behavior during activation by regulating their response to stress, to better respond to the activation at the right time of day, therefore optimizing skeletal muscle regeneration. In conclusion, our study paves the way for the chronobiology of MuSCs, which represents an important step towards the development of cellular chronotherapies in the context of trauma and myopathies.
Funding Source: AFM-Téléthon Agence Nationale de la Recherche (ANR) " MUSCLO" and “European Genomic Institute for Diabetes,” ANR-10-LABX-0046, INSERM CPER-CTRL, Région Hauts-de-France/Fonds Européen de Développement Régional
