Enhanced Secretion of Promyogenic Small Extracellular Vesicles/Exosomes by Quiescent Muscle Cells

ABSTRACT: Skeletal muscle tissue plays a key metabolic role in the organism, partly via signaling to other tissues. Intercellular signaling via small extracellular vesicles (sEV) is emerging as an important mechanism in homeostasis, regeneration and disease, but the roles of sEV derived from muscle cells are poorly defined. In a culture model of physiologically relevant muscle cell states, we observed quantitative differences in secretion of sEV with size ~150 nm and marker profile (Alix, TSG101, flotillin-1, CD9) consistent with exosomes. Unexpectedly, rates of sEV secretion were reversibly increased as myoblasts entered and exited G0, correlating with expression of Kibra, a regulator of EV biogenesis. Perturbation of Kibra led to corresponding alterations of sEV secretion, supporting a role in enhanced sEV biogenesis in G0. Proteomic profiling of sEV revealed a set of proteins common to all muscle cell states, as well as state-specific proteins. Functionally, donor sEV purified from all muscle cell states were able to activate a Wnt reporter in target cells, suggesting preservation of signaling capability. However, only G0-derived sEV were able to induce endogenous myogenic markers and phenotypic differentiation to myotubes. Taken together, we provide evidence that quiescence in myogenic cells is associated with quantitative and qualitative alterations in sEV secretion and signaling function. Given the enhanced secretion and unique signaling properties of sEV from G0 muscle cells in culture, we propose that sEV produced by quiescent muscle stem cells may play an important role in vivo, during muscle homeostasis and regeneration.

INSTRUMENT(S): Orbitrap Exploris 240

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: Swasti Raychaudhuri  

LAB HEAD: Jyotsna Dhawan

PROVIDER: PXD045797 | Pride | 2024-07-09

REPOSITORIES: Pride