Myogenin is an essential regulator of adult myofibre growth and muscle stem cell homeostasis

Ganassi, Massimo; Badodi, Sara; Wanders, Kees; Zammit, Peter S.; Hughes, Simon M.

doi:10.7554/elife.60445

Cited by 102 publications

(73 citation statements)

References 101 publications

(165 reference statements)

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“…These results suggest a reduced fusion index of satellite cells in the absence of Rbm24. This is correlated with the impaired upregulation of myogenin, which was implicated recently as an important regulator of muscle fusion 40 , 41 . Thus, the present results show that Rbm24 is involved in the differentiation of satellite cells into myofibers to repair the damaged tissue.…”

Section: Resultsmentioning

confidence: 88%

“…How myogenin expression is controlled in myoblasts and particularly in activated satellite cells to trigger their fusion into myofibers is a topic of interesting research 40 , 41 . Many proteins have been shown to regulate the timing and cell-type specific transcription of myogenin gene 42 – 44 , but the molecular mechanism governing its post-transcriptional regulation is still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

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Rbm24 displays dynamic functions required for myogenic differentiation during muscle regeneration

Grifone

Saquet

Desgres

et al. 2021

Sci Rep

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Skeletal muscle has a remarkable capacity of regeneration after injury, but the regulatory network underlying this repair process remains elusive. RNA-binding proteins play key roles in the post-transcriptional regulation of gene expression and the maintenance of tissue homeostasis and plasticity. Rbm24 regulates myogenic differentiation during early development, but its implication in adult muscle is poorly understood. Here we show that it exerts multiple functions in muscle regeneration. Consistent with its dynamic subcellular localization during embryonic muscle development, Rbm24 also displays cytoplasm to nucleus translocation during C2C12 myoblast differentiation. In adult mice, Rbm24 mRNA is enriched in slow-twitch muscles along with myogenin mRNA. The protein displays nuclear localization in both slow and fast myofibers. Upon injury, Rbm24 is rapidly upregulated in regenerating myofibers and accumulates in the myonucleus of nascent myofibers. Through satellite cell transplantation, we demonstrate that Rbm24 functions sequentially to regulate myogenic differentiation and muscle regeneration. It is required for myogenin expression at early stages of muscle injury and for muscle-specific pre-mRNA alternative splicing at late stages of regeneration. These results identify Rbm24 as a multifaceted regulator of myoblast differentiation. They provide insights into the molecular pathway orchestrating the expression of myogenic factors and muscle functional proteins during regeneration.

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Section: Resultsmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Rbm24 displays dynamic functions required for myogenic differentiation during muscle regeneration

Grifone

Saquet

Desgres

et al. 2021

Sci Rep

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“…Regarding muscle impairments, the differentiation ability of myoblasts is highly critical for muscle repair and regeneration ( Wernig, 2003 ; Chargé and Rudnicki, 2004 ; Dumont et al, 2015 ; Frontera and Ochala, 2015 ). Both MyoD and myogenin dominate downstream genes involved in the formation and maintenance of different mature muscle fibers ( Asakura et al, 1993 ; Zammit, 2017 ; Ganassi et al, 2020 ). Myotube differentiation process is closely associated with the regulation of muscle-specific gene expression, which is followed by myofiber protein synthesis.…”

Section: Resultsmentioning

confidence: 99%

Taurine Protects C2C12 Myoblasts From Impaired Cell Proliferation and Myotube Differentiation Under Cisplatin-Induced ROS Exposure

Zhou

Huang

et al. 2021

Front. Mol. Biosci.

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In cancer patients, chemotherapeutic medication induces aberrant ROS (reactive oxygen species) accumulation in skeletal muscles, resulting in myofiber degradation, muscle weakness, and even cachexia, which further leads to poor therapeutic outcomes. Acting as an antioxidant, taurine is extensively used to accelerate postexercise muscle recovery in athletes. The antioxidant effects of taurine have been shown in mature myotubes and myofibers but not yet in myoblasts, the myotube precursor. The proliferation and differentiation ability of myoblasts play a very important role in myofiber repair and regeneration, which is usually impaired during chemotherapeutics in cancer patients as well. Here, we explored the effects of taurine supplementation on C2C12 myoblasts exposed to cisplatin-induced ROS. We found that cisplatin treatment led to dramatically decreased cell viability; accumulated ROS level; down-regulated expressions of MyoD1 (myoblast determination protein 1), myogenin, and MHC (myosin heavy chain); and impaired myotube differentiation in myoblasts. Significantly, taurine supplementation protected myoblasts against cisplatin-induced cell viability decrease, promoted cellular ROS clearance, and, most importantly, preserved the expressions of MyoD1, myogenin, and MHC as well as myotube differentiation ability. We further conducted NMR-based metabolomic analysis to clarify the underlying molecular mechanisms. We identified 14 characteristic metabolites primarily responsible for the discrimination of metabolic profiles between cisplatin-treated cells and normal counterparts, including increased levels of BCAAs (branched-chain amino acids: leucine and isoleucine), alanine, glycine, threonine, glucose, ADP (adenosine diphosphate), phenylalanine, and PC (O-phosphocholine), and decreased levels of lysine, β-alanine, choline, GPC (sn-glycero-3-phosphocholine), and myo-inositol. Evidently, taurine supplementation partially reversed the changing trends of several metabolites (isoleucine, threonine, glycine, PC, β-alanine, lysine, and myo-inositol). Furthermore, taurine supplementation promoted the proliferation and myotube differentiation of myoblasts by alleviating cellular catabolism, facilitating GSH (reduced glutathione) biosynthesis, improving glucose utilization and TCA (tricarboxylic acid) cycle anaplerosis, and stabilizing cellular membranes. Our results demonstrated the protective effects of taurine on cisplatin-impaired myoblasts and elucidated the mechanistic rationale for the use of taurine to ameliorate muscle toxicity in clinical chemotherapy cancer patients.

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“…Notably, we also observed major binding events for the pioneer factor PU.1 in C6, this being a master transcriptional regulator in activating many target genes during both myeloid and B-lymphoid development (Turkistany and DeKoter, 2011 ). In addition, transcript factors from the MyoG, MyoD, and Mef families, which are essential for the development of functional skeletal muscle, were found in C4 (Al-Khalili et al, 2004 ; Ganassi et al, 2020 ). Taken together, we provide a high-quality comprehensive dataset to study the regenerative epigenomic dynamics of axolotl limb regeneration.…”

Section: Resultsmentioning

confidence: 99%

An ATAC-seq Dataset Uncovers the Regulatory Landscape During Axolotl Limb Regeneration

Wei

Guo³

et al. 2021

Front. Cell Dev. Biol.

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Myogenin is an essential regulator of adult myofibre growth and muscle stem cell homeostasis

Cited by 102 publications

References 101 publications

Rbm24 displays dynamic functions required for myogenic differentiation during muscle regeneration

Rbm24 displays dynamic functions required for myogenic differentiation during muscle regeneration

Taurine Protects C2C12 Myoblasts From Impaired Cell Proliferation and Myotube Differentiation Under Cisplatin-Induced ROS Exposure

An ATAC-seq Dataset Uncovers the Regulatory Landscape During Axolotl Limb Regeneration

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