Stem Cells and Development Unit Institut Pasteur, Paris

Blueprinting muscle heterogeneity along the body axis

Although skeletal muscles share a basic structural organization, with multinucleated myofibers as the functional unit, an unexpected heterogeneity distinguishes head and trunk muscles. This is manifested by their different embryological origins, innervation patterns, myosin composition and properties of their resident muscle stem cells. The extraocular muscle (EOM) functional unit is composed of 6 muscles that attach to the eyeball, with an spatial arrangement that is highly conserved during evolution. Interestingly, these muscles are spared in many myopathies, including the frequent Duchenne Muscular Dystrophy.
To explore muscle heterogeneity throughout developmental progression from progenitor cells to differentiated myofibers, we employed single-cell and single-nucleus RNA sequencing techniques.
Our findings reveal that EOM myonuclei possess unique structural features and utilize gene regulatory networks that are atypical for muscle tissue. This study is poised to shed light on the developmental and evolutionary origins of the EOM’s distinctive functional characteristics, including their ultra-fast contraction profile and resistance to pathological conditions.

Invitée par Sylvie Rétaux