Human muscle regeneration: calcium-dependent and independent processes
Description: Skeletal muscle regeneration relies on muscle stem cells (MuSC), their activation, proliferation, and differentiation/maturation into myofibres. One of the characteristics of MuSC is their quiescence, which allows cells that have exited the cell cycle to proliferate again following their activation by adequate stimulation.Our laboratory is studying human skeletal muscle regeneration using in vitro system. There, activated MuSC proliferate as myoblasts, differentiate into myotubes, and reform a quiescent stem cell population, called reserve cells. Thus, we can study in vitro both the process of myotube differentiation and the activation of reserve cells. Recently, we improved the culture model to be able to keep the cells for long enough to study the process of maturation. One of our long-standing interests is the role of Ca2+ channels and Ca2+ signalling during myogenesis. We will use this model to decipher the role of both STIM1 isoforms, implicated in Ca2+ entry, during myotube maturation. We generated a mouse lacking specifically the long isoform of STIM1 that will allow us to study the role of STIM1L in adult muscles and during ageing. We will also assess the function of STIM1L in the adaptation to physical exercise. Finally, we investigated reserve cell activation upon serum stimulation and showed that it is a Ca2+-independent process, that requires the presence of a Ca2+ channel, Orai3. We will decipher the mechanism by which Orai3 and its partner(s) regulate reserve cell activation.Specifically, we will study:1. The role of STIM1L during the process of differentiation/maturation of human muscle cells 2. The role of STIM1L in training adaptation in young and aged mice 3. The importance of Orai3 and its partner(s) in the process of muscle stem cell activation.
Amount: CHF 658,600
Funding type: research
Funder scheme: Project funding
Start date: 2023-04-01
End date: 2027-03-31
Investigator: Frieden, Maud
Institution: University of Geneva – GE
Topic: Ion Channels and Receptors
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Funded outputs count: 1
Funder award ID: 215363
OpenAlex ID: G180302175