Regulation and phylogeny of skeletal muscle regeneration

Abstract

One of the most fascinating questions in regenerative biology is why some animals can regenerate injured structures while others cannot. Skeletal muscle has a remarkable capacity to regenerate even after repeated traumas, yet limited information is available on muscle repair mechanisms and how they have evolved. For decades, the main focus in the study of muscle regeneration was on muscle stem cells, however, their interaction with their progeny and stromal cells is only starting to emerge, and this is crucial for successful repair and reestablishment of homeostasis after injury. In addition, numerous murine injury models are used to investigate the regeneration process, and some can lead to discrepancies in observed phenotypes. This review addresses these issues and provides an overview of the some of the main regulatory cellular and molecular players involved in skeletal muscle repair.Key words: skeletal muscle, regeneration, stem cells, evolution, quiescence, injury IntroductionThe ability to regenerate tissues and structures is a prevalent feature of metazoans although there is significant variability among species ranging from limited regeneration of a tissue (birds and mammals) to regeneration involving the entire organism (cnidarians, planarians, hydra). The intriguing evolutionary loss of regenerative capacity in more complex organisms highlights the importance of identifying the underlying mechanisms responsible for these diverse regenerative strategies. One of the most studied tissues that contributes to new appendage formation is skeletal muscle, thereby making it a major focus of regeneration studies during evolution. The emergence of new lineage-tracing tools in different animal models has permitted the identification of specific progenitor cell populations and their contribution to tissue repair.Skeletal muscles allow voluntary movement and they play a key role in regulating metabolism and homeostasis in the organism. In mice and humans this tissue represents about 30-40% of the total body mass. This tissue provides an excellent tractable model to study regenerative myogenesis and the relative roles of stem and stromal cells following a single, or repeated rounds of injury. Although muscle regeneration relies mainly on its resident muscle stem (satellite) cells (MuSCs) to effect muscle repair, interactions with neighbouring stromal cells, by direct contact or via the release of soluble factors, is essential to restore proper 3 function. Each step of the myogenic process is regulated by specific regulatory factors including extrinsic cues, yet the nature and source of these signals remain unclear. This review will address these issues and discuss the different experimental models used to investigate the regenerative process. Prenatal and postnatal skeletal muscle developmentIn amniotes, skeletal muscles in the limbs and trunk arise from somites through a series of successive waves that include embryonic and foetal phases of myoblast production (Biressi et al., 2007;Comai and Tajbakhsh, 201...

Syndecan‐4 influences mammalian myoblast proliferation by modulating myostatin signalling and G1/S transition

“…Skeletal muscle is constantly renewed in response to injury, exercise, or muscle diseases. A population of resident stem cells (satellite cells) accounts for skeletal muscle plasticity, maintenance and regeneration [1][2][3]. The muscle progenitor satellite cells are mitotically and physiologically quiescent in healthy muscle; they are stimulated by local damage to proliferate extensively and form myoblasts that will subsequently differentiate and fuse to form muscle fibres.…”

The regenerating skeletal muscle niche guides muscle stem cell self-renewal

“…Skeletal muscle is made up of large multi-nucleated, post mitotic fibers, that have a large reserve capacity to regenerate following injury (Baghdadi & Tajbakhsh, 2018;Dumont, Bentzinger, Sincennes, & Rudnicki, 2015;Fukada, 2018;Wosczyna & Rando, 2018). Skeletal muscle regeneration is driven by skeletal muscle stem cells (MuSCs), typically quiescent in uninjured muscle but following injury, leave G0, enter the cell cycle as myoblasts and expand as needed to repair muscle injuries.…”

Differential physiological role of BIN1 isoforms in skeletal muscle development, function and regeneration

“…We used notexin-induced muscle regeneration in Bin1x11-/-mice and observed a decrease in fiber crosssectional area at 14 and 28 days after the muscle damage associated with a reduced fusion index and eventually leading to a decrease in specific force recovery. A deficit in myofibers growth during early regeneration was previously linked to a defect in myoblast fusion (Millay et al 2014;Baghdadi and Tajbakhsh 2018). Additionally, BIN1 was abundant at the myotubes fusion sites (Klinge et al 2007) and C2C12 cells expressing antisense Bin1 showed an impaired myoblast fusion (Wechsler-Reya et al 1998).…”