Control of Skeletal Muscle Stem Cell Proliferation

Abstract

Skeletal muscle has high capacity to regenerate and compensate for muscle wear and tear, due to the activity of skeletal muscle stem cells (MuSCs). They require a tight balance between several intrinsic and extrinsic regulators to maintain MuSCs quiescence in normal conditions and producing the amount of progenitor cell sufficient to compensate for the lost cells and replenish the stem cell pool after an injury. Using pharmacological and genetic approaches to cause loss-of-function in hedgehog (Hh) signalling, we suggest that quiescent MuSCs are refractory to Hh signalling. We show that levels of Hh signalling controls MuSCs activation and progression through the cell cycle. RNA-sequencing techniques identifies some of Hh target genes that are associated with DNA replication and MuSCs proliferation. Minichromosome maintenance complex genes (mcm) might have other functions than DNA replication. Our findings support the claim that Hh plays a direct role in MuSCs activation and proliferation.