Stem cells play a central role in development and maintenance of tissues and organs in the body of animals and humans. During growth or regeneration, skeletal muscle cells are unable to divide but replenish from a population of progenitor stem cells, which have the unique ability to divide, to produce copies of themselves as well as differentiated muscle cells. Muscle differentiation is a coordinated process of tissue-specific gene expression and irreversible cell cycle exit. Failure or dysregulations of these processes either lead to apoptosis or cancer.
The team leader has identified and characterized a novel major progenitor stem cell population which gives rise to nearly all skeletal muscle cells, including the myogenic stem cell population of the adult, and identified key transcription regulators (Pax3 and Pax7) implicated in survival, specification and proliferation of these cells.
The overall aims of our research project are to :
Identify the transciptional networks involved in muscle cell specification and cell cycle growth arrest, both during the irreversible terminal differentiation of myogenic cells during development, and in the acquisition of reversible quiescence of adult muscle progenitor cells.
Identify the upstream regulators of the p21cip1 and p57kip2 genes which are key regulators of cell cycle exit in vivo and the functions of Pax3/Pax7 in this context. Understand the functions of Pax3 and Pax7 during myogenesis, development and evolution as well as unravel the molecular mechanisms underlying dysregulation of the PAX function that leads to the alveolar rhabdomyosarcoma paediatric myogenic tumor formation in vivo. Understanding the signals and molecular regulation ensuring the maintainance of a pool of mitotic progenitor cells, and how these cells are instructed when to commit to the myogenic lineage or to self-renew is of major importance in using muscle progenitor stem cells for muscle repair and to treat muscle pathological conditions (regenerative or reparative medicine), as well as to develop new therapeutic strategies for the treatment of cancers.
