Cellular Heterogeneity in Physiological and Pathological Myogenesis

From embryonal development to adulthood and aging, the skeletal muscle stem cell (MuSC) population is endowed with functional capacities to face changing conditions throughout the lifespan, operating under different stress types, including its involvement in muscle repair. A genetic and functional heterogeneity allows various types of stem cells to oscillate between different phenotypic and functional states. The cellular plasticity of the MuSC population provides the basis of the ability to adapt to varying requirements during skeletal muscle growth, homeostasis, regeneration, and resistance to unfavorable conditions. Such dynamic heterogeneity determines the fate asymmetry of the MuSC population, one of the key factors regulating the balance between self-renewal and differentiation.

Exploring the genetic and non-genetic factors underlying and determining MuSC heterogeneity is essential to fully understand the behavior of this cell population during development, homeostasis, regeneration, and aging. Study of this feature ranges from investigating (1) the hierarchy and stochasticity in gene expression and signaling pathways; (2) the different characteristics of the niche observed in homeostasis and regeneration (i.e., polarized vs. non-polarized niche); (3) the complex crosstalk of MuSCs with the surrounding matrix; (4) how the reversible fluctuations among different cell cycle states (quiescence, activation, proliferation) and the mechano-sensitivity influence the cell morphology and vice versa; (5) how the extent of microenvironmental stability and instability affects the cell population exposed to various soluble signals; (6) how the presence of multiple cell populations and their heterogeneity affect MuSC heterogeneity and their ability to maintain the balance between self-renewal and differentiation.

Shedding light on the molecular mechanisms and fundamental aspects of stem cell heterogeneity is a challenge for the clinical applications or the pharmacological manipulation of such a promising cellular tool for regenerative medicine approaches.

The purpose of this Research Topic is to collect recent research and methodological advances related to the different aspects of muscle cell heterogeneity during development, acute and chronic repair, and aging. The central focus will be on muscle stem cell heterogeneity and plasticity in terms of:


• hierarchy and stochasticity in gene expression and signaling pathways
• molecular and epigenetic signature and mechanisms
• cell morphology
• response to microenvironment changing
• cellular crosstalk with tissue-resident and recruited muscle cell populations