Muscles are extremely used in our daily life. To work properly they need to be continuously maintained and regenerated. This remarkable regenerative capability is mainly due to a resident muscle stem cells (MuSC) population, also known as Satellite Cells. These cells are dormant but can be activated to restore the damaged muscles. We are particularly interested in understanding how MuSC behave upon injury and what are the genes controlling their behavior.
For our research, we use Drosophila as a model, which has long been a fruitful paradigm to study myogenesis; both the muscle structure and core myogenic programs being highly conserved between flies and mammals. MuSCs have recently been identified in the flies and we developed novel transgenic tools and imaging approaches to both in vivo track MuSCs and identify genes regulating their behavior.
Early MuSC activation ?
Muscle damages lead to the activation of MuSCs, that migrate towards the site of injury and provide differentiated myoblasts that repair the muscle. We use live imaging and a membrane tagged MuSC reporters to uncover the initial key steps of MuSCs activation as they leave their niche, including their migration, remodelling and interactions with other cell types.
Image adapted from Gunage RD et al., 2017
How MuSC sense signals from their environment ?
MuSC activation involves instructive signals from the microenvironment and a key player is Notch, which is required for both maintenance and proliferation of MuSCs. Notch is also involved in the fate-shifting choice between stemness and differentiation. We are investigating how MuSCs sense and respond to Notch across the successive steps of muscle repair. We use live imaging methods to simultaneously track both Notch activity in MuSCs and the source of ligands, during muscle repair.
Genes and programs required for MuSC activation ?
We combine large scale-sequencing and RNAi screening approaches to identify genes specifically active in MuSC prior to, and in response to muscle injury, in order to determine which programs 1) prevent MuSC to differentiate in normal physiological conditions and 2) control the different steps of MuSC activation and activity during muscle repair.