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Our goal is to identify new functions for the cells located in the microenvironment of muscle cells beside their canonical properties (e.g., regulation of inflammation for macrophages, supply of oxygen and nutriments for vessel cells) and how muscle stem cells and myofibers are controlled by their closest environment in both normal and pathological contexts. The identification of new molecules or novel functions of already known pathways are the basis for expanding our current understanding about skeletal muscle homeostasis and its pathophysiology.
Stem cells are important in the maintenance and repair of many tissues all along the life span. It is the case in skeletal muscle, which presents high plasticity and regenerative properties to keep constant physiological parameters (homeostasis). Normal skeletal muscle mobilizes tissue-associated endogenous stem cells, mainly satellite cells, to repair damaged myofibers. Indeed, muscle stem cells sustain regeneration that is crucial for muscle homeostasis, as well as the self-renewal mechanisms that maintain their pool constant.
A key issue we address is the tissue environment in which muscle stem cells are activated. Environment plays important roles in the behavior of muscle stem cells and myogenic cells, although the mechanisms are poorly unknown. Various cell types in the vicinity of stem cells communicate with each other to correctly drive regeneration. We explore the roles of immune cells (inflammation), endothelial and peri-endothelial cells (angiogenesis) and interstitial cells (fibrosis) on myogenic cell fate in normal healthy regenerating muscle and during muscular dystrophies. Indeed, myopathies are characterized by the alteration in the environment of muscle stem cells, such as the presence of chronic inflammation and fibrosis, which are detrimental for both tissue repair and cell therapies.