Muscle development and muscle stem cells

Subproject Speakers
Berlin: Carmen Birchmeier, PhD, Prof.
Paris:  Frédéric Relaix, PhD, Prof.
 

During skeletal muscle development, a Pax7+ progenitor cell population is established, which contributes to muscle growth and generates satellite cells late in fetal development [1]. Satellite cells are responsible for skeletal muscle regeneration, and represent the stem cell of the adult muscle [2]. Similarities between pathways that control progenitor or satellite cell renewal and differentiation are apparent. For instance, myogenic determination factors like Myf5 and MyoD control myogenic differentiation of progenitor and satellite cells. The ability to manipulate the molecular mechanisms that control proliferation, self-renewal, and myogenic differentiation has important implications for the use of satellite cells in regenerative medicine for skeletal muscle diseases. Several signaling systems, for instance Notch, BMPs, and tyrosine kinases, control proliferation of progenitors and satellite cells, and affect the balance between progenitor or satellite cell expansion and differentiation. Our previous work allows us to design strategies to manipulate adult muscle growth in a muscle stem cell-dependent and -independent manner. Moreover, we are now able to manipulate crucial muscle stem cell properties, like proliferation and differentiation, by using signaling molecules. These are pivotal tools towards the development of stem cell therapies for neuromuscular disorders. The major focus of this project is to develop strategies that recruit and expand the inherent muscle stem cell pool, which is precociously exhausted during muscular dystrophies, resulting in uncompensated muscle wasting of the affected individuals.

Completed theses