Abstract
Satellite stem cell availability and high regenerative capacity have made them an ideal therapeutic approach for muscular dystrophies and neuromuscular diseases. Adult satellite stem cells remain in a quiescent state and become activated upon muscular injury. A series of molecular mechanisms succeed under the control of epigenetic regulation and various myogenic regulatory transcription factors myogenic regulatory factors, leading to their differentiation into skeletal muscles. The regulation of MRFs via various epigenetic factors, including DNA methylation, histone modification, and non-coding RNA, determine the fate of myogenesis. Furthermore, the development of histone deacetylation inhibitors (HDACi) has shown promising benefits in their use in clinical trials of muscular diseases. However, the complete application of using satellite stem cells in the clinic is still not achieved. While therapeutic advancements in the use of HDACi in clinical trials have emerged, histone methylation modulations and the long non-coding RNA (lncRNA) are still under study. A comprehensive understanding of these other significant epigenetic modulations is still incomplete. This review aims to discuss some of the current studies on these two significant epigenetic modulations, histone methylation and lncRNA, as potential epigenetic targets in skeletal muscle regeneration. Understanding the mechanisms that initiate myoblast differentiation from its proliferative state to generate new muscle fibres will provide valuable information to advance the field of regenerative medicine and stem cell transplant.
Highlights
Skeletal muscle cells were once understood to have locomotive function only, but advances in medicine and research have shown their essential role beyond just locomotive function
There is a compelling association between various diseases and skeletal muscles, including HIV, neuromuscular diseases, cancer, heart failure, and chronic infectious diseases that induce muscle atrophy, known as cachexia
For satellite stem cell transplantation in regenerative medicine to have a successful clinical application, it is imperative to understand the underlying mechanisms that govern these cells from their quiescent state into fully matured myofiber cells
Summary
Skeletal muscle cells were once understood to have locomotive function only, but advances in medicine and research have shown their essential role beyond just locomotive function. Various studies have documented their crucial role as an endocrine organ that secretes various proteins, like myokines, that regulate energy production and consumption (Iizuka et al, 2014; Giudice and Taylor, 2017) They are believed to possess anti-tumour protective properties (Stölting et al, 2013). Inoculation with a high number of stem cells increases the body’s stress response which activates a strong immune response and further causes a reduction in the oxygen and nutrition supply of the body (Kuang and Rudnicki, 2008). These failing limitations did not discourage the search into exploring more improved therapies in the use of satellite stem cell therapy. Histone modification and lncRNA modulation have shown progressive studies in the regulation of myogenesis and appear to be promising potential new targets in degenerative muscle diseases and muscular repair
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