**High-Dimensional Single-Cell Quantitative Profiling of Skeletal Muscle Cell Population Dynamics during Regeneration**

**Lucia Lisa Petrilli 1,2,**†**, Filomena Spada 1,**†**, Alessandro Palma 1, Alessio Reggio 1, Marco Rosina 1, Cesare Gargioli 1, Luisa Castagnoli 1, Claudia Fuoco 1,\* and Gianni Cesareni 1,3**


Received: 17 April 2020; Accepted: 14 July 2020; Published: 18 July 2020

**Abstract:** The interstitial space surrounding the skeletal muscle fibers is populated by a variety of mononuclear cell types. Upon acute or chronic insult, these cell populations become activated and initiate finely-orchestrated crosstalk that promotes myofiber repair and regeneration. Mass cytometry is a powerful and highly multiplexed technique for profiling single-cells. Herein, it was used to dissect the dynamics of cell populations in the skeletal muscle in physiological and pathological conditions. Here, we characterized an antibody panel that could be used to identify most of the cell populations in the muscle interstitial space. By exploiting the mass cytometry resolution, we provided a comprehensive picture of the dynamics of the major cell populations that sensed and responded to acute damage in wild type mice and in a mouse model of Duchenne muscular dystrophy. In addition, we revealed the intrinsic heterogeneity of many of these cell populations.

**Keywords:** single-cell; mass cytometry; skeletal muscle regeneration; skeletal muscle homeostasis; fibro/adipogenic progenitors; myogenic progenitors; muscle populations
