Régulation des cellules souches musculaires par leur microenvironnement

 

Conrad Florian Bentzinger

Université de Sherbrooke

 

Domaine : génétique humaine (organisme vivants)

Programme chercheurs-boursiers - Junior 2

Concours 2017-2018

Stem cells that are responsible for maintenance and repair of adult tissues are dependent on regulatory cues from their microenvironment, often referred to as the niche. Niche components consist for instance of locally secreted growth factors, large structural adhesion molecules and cell surface receptors presented by different cell types residing in the tissues. In skeletal muscle tissue, stem cells are particularly sensitive to changes in their niche and fundamental properties of these cells, such as their ability to divide, to persist in the tissue over time and their capacity for repairing damaged muscle fibers, are largely determined by the composition of the niche.

Diseases of the musculature are accompanied by changes in the niche that negatively affect stem cell function. Likewise, alterations in the stem cell microenvironment underlie the impaired healing capacity of muscle tissue that accompanies aging and certain multisystemic conditions. Moreover, deregulated niche signals also appear to be critical determinants of the malignancy of stem-like cells in muscle tumors. In spite of its fundamental role in tissue regeneration and disease, the architecture as well as the integration of regulatory signals in the muscle stem cell niche remain poorly understood.

Over the next four years, we propose to study the role of key niche components and cell populations and to elucidate how these regulatory mechanisms are perturbed in pathophysiological conditions.