It takes all kinds: heterogeneity among satellite cells and fibro-adipogenic progenitors during skeletal muscle regeneration

ABSTRACT Vertebrate skeletal muscle is composed of multinucleate myofibers that are surrounded by muscle connective tissue. Following injury, muscle is able to robustly regenerate because of tissue-resident muscle stem cells, called satellite cells. In addition, efficient and complete regeneration depends on other cells resident in muscle – including fibro-adipogenic progenitors (FAPs). Increasing evidence from single-cell analyses and genetic and transplantation experiments suggests that satellite cells and FAPs are heterogeneous cell populations. Here, we review our current understanding of the heterogeneity of satellite cells, their myogenic derivatives and FAPs in terms of gene expression, anatomical location, age and timing during the regenerative process – each of which have potentially important functional consequences.

Drosophila Activin signaling promotes muscle growth through InR/dTORC1 dependent and independent processes

The Myostatin/Activin branch of the TGFβ superfamily acts as a negative regulator of vertebrate skeletal muscle size, in part, through downregulation of insulin/IGF-1 signaling. Surprisingly, recent studies in Drosophila indicate that motoneuron derived Activin signaling acts as a positive regulator of muscle size. Here we demonstrate that Drosophila Activin signaling promotes growth of the muscle cells along all three axes; width, thickness and length. Activin signaling positively regulates the InR/dTORC1 pathway and the level of Mhc, an essential sarcomeric protein, via increased Pdk1 and Akt1 expression. Enhancing InR/dTORC1 signaling in the muscle of Activin pathway mutants restores Mhc levels close to wild-type, but only increases muscle width. In contrast, hyperactivation of the Activin pathway in muscles increases overall larval body and muscle fiber length even when Mhc levels were lowered by suppression of dTORC1. Together, these results indicate that the Drosophila Activin pathway regulates larval muscle geometry and body size via promoting InR/dTORC1-dependent Mhc production and the differential assembly of sarcomeric components into either pre-existing or new sarcomeric units depending on the balance of InR/dTORC1 and Activin signals.

A Novel Analysis of the Peptide Terminome Characterizes Dynamics of Proteolytic Regulation in Vertebrate Skeletal Muscle Under Severe Stress

In healthy cells, proteolysis is orderly executed to maintain basal homeostasis and normal physiology. Dyscontrol in proteolysis under severe stress condition induces cell death, but the dynamics of proteolytic regulation towards the critical phase remain unclear. Teleosts have been suggested an alternative model for the study of proteolysis under severe stress. In this study, horse mackerel (Trachurus japonicus) was used and exacerbated under severe stress conditions due to air exposure. Although the complete genome for T. japonicus is not available, a transcriptomic analysis was performed to construct a reference protein database, and the expression of 72 proteases were confirmed. Quantitative peptidomic analysis revealed that proteins related to glycolysis and muscle contraction systems were highly cleaved into peptides immediately under the severe stress. Novel analysis of the peptide terminome using a multiple linear regression model demonstrated profiles of proteolysis under severe stress. The results indicated a phase transition towards dyscontrol in proteolysis in T. japonicus skeletal muscle during air exposure. Our novel approach will aid in investigating the dynamics of proteolytic regulation in skeletal muscle of non-model vertebrates.

The likely effects of thermal climate change on vertebrate skeletal muscle mechanics with possible consequences for animal movement and behaviour

Changes in temperature, caused by climate change, can alter the amount of power an animal’s muscle produces, which could in turn affect that animal’s ability to catch prey or escape predators. Some animals may cope with such changes, but other species could undergo local extinction as a result.