Mapping Facioscapulohumeral muscular dystrophy through single nuclei RNA sequencing

Investigator: Giorgio Tasca PhD

Category: Research - Basic

During the progression of FSHD, muscle fibers are destroyed and replaced by fat and connective tissue leading to irreversible muscle weakness. Although the genetic lesion associated with FSHD, which causes the aberrant activation of the DUX4 gene in skeletal muscle, has been characterized more than 10 years ago, the exact mechanism leading to muscle damage, the molecular pathways that are sequentially activated during the progression of the disease and the cells responsible for that detrimental process remain largely unknown. This information is key to identify new targets for therapies to reduce the consequences of the disease.

With this study we will characterize the phenomena taking place in muscles with different stages of involvement identified by muscle magnetic resonance imaging (MRI), including normal, inflamed and fatty replaced muscles, to establish a temporal and spatial map of the molecular changes leading to muscle damage using cutting-edge genomic techniques. Leveraging the unprecedented resolution of these techniques, it will be possible to dissect and correctly localize the events in the specific cells of the muscle biopsies and put them in the temporal framework provided by MRI.