Mechanisms controlling muscle stem cell (MuSC) fate are not yet fully known and include both autonomous and non-autonomous processes. Our team aims to identify the role of metabolism and the metabolic environment of MuSC during its fate progression, as well as the role of key metabolic regulators such as AMPK. By unraveling the dynamic regulations between metabolism and MuSC fate, we finally aim to determine its role in skeletal muscle homeostasis, skeletal muscle plasticity, and the development of diseases
Although skeletal muscle metabolism is generally considered at the muscle fiber scale, it is now clear that metabolism also plays an important role in the functioning of the muscle stem cell (MuSC). In particular, the key cellular functions of metabolism (i.e. energy production, macromolecule synthesis, elimination of degraded macromolecules/organelles, substrate production and extraction, and renewal of cell components) can modulate the steps of the MuSC fate: quiescence, activation, proliferation/expansion, differentiation, fusion, and self-renewal/dormancy. To address “metabolic stemness” (i.e. distinct metabolic characteristics of MuSC states), we propose a metabolomic approach to perform an in-depth analysis of the metabolism of stem cells. Metabolomics enables the characterization of endogenous small molecules revealing connections between different pathways that actually operate within a living cell. Whereas significant effort has focused on using synthetic small molecules to control MuSC function, our metabolomic study will identify novel skeletal muscle-specific metabolites (i.e. endogenous molecules) that modulate MuSC fate and skeletal muscle homeostasis.
AMPK and AMPK-related kinases are key metabolic sensors, and central coordinators of cellular metabolism. Therefore, we aim to decipher their role in the regulation of MuSC fate and adult myogenesis. In particular, we aim at understand their role in the maintenance of the MuSC pool through the regulation of cell division and self-renewal.
We will decipher the role of AMPK and NUAK1-dependent pathways in the splicing deregulation associated with DM1. In addition, our goal is to establish the potential of AMPK and/or NUAK1 activation in managing DM1 symptoms, in particular skeletal muscle atrophy and mitochondrial dysfunction, and to provide leads towards novel therapeutic strategies for DM1.
UCBL – CNRS UMR 5261 – INSERM U1314
Faculté de Médecine et de Pharmacie – 3ème étage – Aile AH
8 avenue Rockefeller