Long non-coding RNAs (lncRNAs) are important regulators of diverse biological processes. Here we report on functional identification and characterization of a novel long intergenic non-coding RNA ...with MyoD-regulated and skeletal muscle-restricted expression that promotes the activation of the myogenic program, and is therefore termed Linc-RAM (Linc-RNA Activator of Myogenesis). Linc-RAM is transcribed from an intergenic region of myogenic cells and its expression is upregulated during myogenesis. Notably, in vivo functional studies show that Linc-RAM knockout mice display impaired muscle regeneration due to the differentiation defect of satellite cells. Mechanistically, Linc-RAM regulates expression of myogenic genes by directly binding MyoD, which in turn promotes the assembly of the MyoD-Baf60c-Brg1 complex on the regulatory elements of target genes. Collectively, our findings reveal the functional role and molecular mechanism of a lineage-specific Linc-RAM as a regulatory lncRNA required for tissues-specific chromatin remodelling and gene expression.
Nuclear positioning in skeletal muscle Roman, William; Gomes, Edgar R.
Seminars in cell & developmental biology,
October 2018, 2018-10-00, 20181001, Volume:
82
Journal Article
Peer reviewed
Open access
Skeletal muscle cells possess a unique cellular architecture designed to fulfill their contractile function. Muscle cells (also known as myofibers) result from the fusion of hundreds of myoblasts and ...grow into a fiber of several centimeters in length. Cellular structures gradually become organized during muscle development to raise a mature contractile cell. A hallmark of this singular cell architecture is the position of nuclei at the periphery of the myofiber, below the plasma membrane. Nuclei in myofibers are evenly distributed except in specialized regions like the neuromuscular or myotendinous junctions. Disruption of nuclear positioning results in hindered muscle contraction and occurs in a multitude of muscle disorders as well as in regenerative myofibers. We will explore in this review the step by step nuclear migrations during myogenesis for nuclei to reach their evenly distributed anchored position at the periphery.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Mutations in genes encoding nuclear envelope (NE) proteins, despite being rare, represent a major threat to cell homeostasis by compromising nuclear integrity and function as well as ...nucleocytoplasmic communication. In the last decade, several diseases have been associated to mutations in the TOR1AIP1 gene that codes for lamina-associated polypeptide 1 (LAP1), a NE protein ubiquitously expressed in human tissues. Although this is suggestive of an important physiological role of LAP1, it remains unclear which cellular activities are regulated by this protein. To address this, we investigated the molecular repercussions of its deficiency in patient-derived skin fibroblasts carrying a pathological LAP1 mutation (p.E482A), previously reported in a case of severe dystonia, cerebellar atrophy and cardiomyopathy. Using liquid chromatography with tandem mass spectrometry (LC–MS/MS), a quantitative proteome analysis was performed to identify up-/downregulated proteins in LAP1 E482A fibroblasts relative to age-matched control fibroblasts. A subsequent functional characterization of the LC–MS/MS-identified differentially expressed proteins using bioinformatics tools unraveled various signaling pathways/biological processes potentially deregulated in LAP1 E482A fibroblasts, such as DNA repair, neurodevelopment and myogenesis, among others. This work sheds light on dysfunctional molecular mechanisms in LAP1-deficient cells, which will contribute to a better understanding of LAP1’s physiological relevance for the maintenance of cell homeostasis and, hopefully, allow the identification of potential therapeutic targets for LAP1-associated pathologies.
Inflammation is usually considered as harmful; however, it is also necessary for tissue recovery after injury. Macrophages exert immune and nonimmune functions throughout this process. During ...skeletal muscle regeneration, they mount an inflammatory response while exerting trophic roles on muscle and mesenchymal stem cells. Proinflammatory macrophages shift to being anti-inflammatory, triggering the resolution of inflammation. Studies have highlighted that during this shift, a crosstalk ensues, integrating cues for resolution, efferocytosis, cellular metabolism, and signaling pathways. During the restorative phase, macrophages dampen inflammation while promoting stem cell differentiation, angiogenesis, and matrix remodeling. Since blunting the inflammatory phase can be detrimental for muscle regeneration, we suggest that rather than fighting inflammation, it should be allowed to operate and resolve, thus allowing for tissue recovery.
Macrophages are key orchestrators of the inflammatory response after tissue injury. They do so by controlling both proinflammatory and restorative/anti-inflammatory phases, and by sequentially exerting a variety of functions impacting on parenchymal, vascular, and fibroblastic cells.The resolution of inflammation is mandatory for tissue repair and consists of shifting the inflammatory status of macrophages from a pro- towards an anti-inflammatory/restorative profile. It is mainly operated by macrophages through efferocytosis, that is, phagocytosis of dead cells and debris.The shift occurring in macrophage inflammatory status and the resolution of inflammation are controlled by integrating early inflammation-resolving cues, efferocytosis, rewiring of cellular metabolism, and activation of specific intracellular signaling pathways.We posit that while the proinflammatory phase is shorter and less intense after tissue injury than during a given infection, this natural response should not be blunted. In injured skeletal muscle, applying an anti-inflammatory treatment too early can be detrimental in returning to homeostasis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cultured meat forms part of the emerging field of cellular agriculture. Still an early stage field it seeks to deliver products traditionally made through livestock rearing in novel forms that ...require no, or significantly reduced, animal involvement. Key examples include cultured meat, milk, egg white and leather. Here, we focus upon cultured meat and its technical, socio-political and regulatory challenges and opportunities.
The paper reports the thinking of an interdisciplinary team, all of whom have been active in the field for a number of years. It draws heavily upon the published literature, as well as our own professional experience. This includes ongoing laboratory work to produce cultured meat and over seventy interviews with experts in the area conducted in the social science work.
Cultured meat is a promising, but early stage, technology with key technical challenges including cell source, culture media, mimicking the in-vivo myogenesis environment, animal-derived and synthetic materials, and bioprocessing for commercial-scale production. Analysis of the social context has too readily been reduced to ethics and consumer acceptance, and whilst these are key issues, the importance of the political and institutional forms a cultured meat industry might take must also be recognised, and how ambiguities shape any emergent regulatory system.
•Cellular agriculture includes tissue engineering and fermentation based approaches.•Five key technical challenges with cultured meat production are made explicit.•Social issue studies disproportionately focus upon ethics and consumer acceptance.•New analysis of political, institutional and regulatory issues is required.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
•Seven fgfr genes were identified in spotted sea bass genome.•fgfr4 was the most expressed fgfr during myoblast proliferation and differentiation.•fgfr4 showed co-expression with marker gene of ...skeletal muscle satellite cells.•Fgfr4 exhibits the differentiation process of myoblasts in spotted sea bass.
Fibroblast growth factor receptors (Fgfrs) are involved in cell proliferation, differentiation, and migration via complex signaling pathways in different tissues. Our previous studies showed that fibroblast growth factor receptor 4 (fgfr4) was detected in the most significant quantitative trait loci (QTL) for growth traits. However, studies focusing on the function of fgfr4 on the growth of bony fish are still limited. In this study, we identified seven fgfr genes in spotted sea bass (Lateolabrax maculatus) genome, namely fgfr1a, fgfr1b, fgfr2, fgfr3, fgfr4, fgfr5a, and fgfr5b. Phylogenetic analysis, syntenic analysis and gene structure analysis were conducted to further support the accuracy of our annotation and classification results. Additionally, fgfr4 showed the highest expression levels among fgfrs during the proliferation and differentiation stages of spotted sea bass myoblasts. To further study the function of fgfr4 in myogenesis, dual-fluorescence in situ hybridization (ISH) assay was conducted, and the results showed co-localization of fgfr4 with marker gene of skeletal muscle satellite cells. By treating differentiating myoblasts cultured in vitro with BLU-554, the mRNA expressions of myogenin (myog) and the numbers of myotubes formed by myoblasts increased significantly compared to negative control group. These results indicated that Fgfr4 inhibits the differentiation of myoblasts in spotted sea bass. Our findings contributed to filling a research gap on fgfr4 in bony fish myogenesis and the theoretical understanding of growth trait regulation of spotted sea bass.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Skeletal muscle in vertebrates is formed by two major routes, as illustrated by the mouse embryo. Somites give rise to myogenic progenitors that form all of the muscles of the trunk and limbs. The ...behavior of these cells and their entry into the myogenic program is controlled by gene regulatory networks, where paired box gene 3 (Pax3) plays a predominant role. Head and some neck muscles do not derive from somites, but mainly form from mesoderm in the pharyngeal region. Entry into the myogenic program also depends on the myogenic determination factor (MyoD) family of genes, but Pax3 is not expressed in these myogenic progenitors, where different gene regulatory networks function, with T-box factor 1 (Tbx1) and paired-like homeodomain factor 2 (Pitx2) as key upstream genes. The regulatory genes that underlie the formation of these muscles are also important players in cardiogenesis, expressed in the second heart field, which is a major source of myocardium and of the pharyngeal arch mesoderm that gives rise to skeletal muscles. The demonstration that both types of striated muscle derive from common progenitors comes from clonal analyses that have established a lineage tree for parts of the myocardium and different head and neck muscles. Evolutionary conservation of the two routes to skeletal muscle in vertebrates extends to chordates, to trunk muscles in the cephlochordate Amphioxus and to muscles derived from cardiopharyngeal mesoderm in the urochordate Ciona, where a related gene regulatory network determines cardiac or skeletal muscle cell fates. In conclusion, Eric Davidson’s visionary contribution to our understanding of gene regulatory networks and their evolution is acknowledged.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Aquaculture has become an agronomic activity with noticeable development around the world to respond to the simultaneous decrease of fish captures and the increasing demand of aquatic products for ...human consumption. However, different problems limit the development of this industry and one of those is the time required for most of the cultured fish species to achieve economically viable the commercial size. The knowledge up to date of the regulatory systems involved in controlling growth has improved very much but, it is still necessary to devote efforts to transform the basic information in application to fish culture production. The aim of the present review is to summarize the knowledge acquired with the studies about the GH/IGF axis and other hormones regarding their function on the regulation of fish muscle development and growth. To this end, GH and IGFs effects in muscle cells on metabolism and development are examined, as well as the contribution of IGF-I binding proteins, IGF-I receptors and their downstream regulated molecules like TOR and its relation with cell proliferation and differentiation and the myogenic regulatory factors. The effect of regulatory molecules on cultured myocytes are reviewed as well as in vivo responses, including the model of sustained and maintained swimming. Key aspects we consider should be further investigated to complete the scenario of the regulation of fish muscle are also proposed.
•The GH/IGF axis regulates growth and metabolism in fish muscle•Thyroid hormones and steroids exert important roles controlling muscle growth•IGF-I and IGF-II stimulate nutrients uptake and differentially regulate myogenesis•TOR and proteolytic systems' members can be valuable markers of growth condition•Moderate and sustained swimming provokes in fish better growth and flesh quality
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Skeletal myogenesis is a highly coordinated process that involves cell proliferation, differentiation and fusion controlled by a complex gene regulatory network. The microRNA gene cluster miR-17–92 ...has been shown to be related to this process; however, the exact role of each cluster member remains unclear. Here, we show that miR-17 and miR-20a could effectively promote the differentiation of both C2C12 myoblasts and primary bovine satellite cells. In contrast, miR-18a might play a negative role in C2C12 cell differentiation, while miR-19 and miR-92a had little influence. Transcriptome and target analyses revealed that miR-17 could act on
Ccnd2
,
Jak1
and
Rhoc
genes that are critical for cell proliferation and/or fusion. Notably, the addition of miR-19 could reverse the lethal effect of miR-17 and could thus facilitate the maturation of myotubes. Furthermore, by co-injecting the lentiviral shRNAs of miR-17 and miR-19 into mouse tibialis anterior muscles, we demonstrated the wound healing abilities of the two miRNAs. Our findings indicate that in combination with miR-19, miR-17 is a potent inducer of skeletal muscle differentiation.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The Myogenic Regulatory Factors (MRFs) Myf5, MyoD, myogenin and MRF4 are members of the basic helix-loop-helix family of transcription factors that control the determination and differentiation of ...skeletal muscle cells during embryogenesis and postnatal myogenesis. The dynamics of their temporal and spatial expression as well as their biochemical properties have allowed the identification of a precise and hierarchical relationship between the four MRFs. This relationship establishes the myogenic lineage as well as the maintenance of the terminal myogenic phenotype. The application of genome-wide technologies has provided important new information as to how the MRFs function to activate muscle gene expression. Application of combined functional genomics technologies along with single cell lineage tracing strategies will allow a deeper understanding of the mechanisms mediating myogenic determination, cell differentiation and muscle regeneration.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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