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myoblast fusion

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https://www.readbyqxmd.com/read/28188264/immortalized-human-myotonic-dystrophy-muscle-cell-lines-to-assess-therapeutic-compounds
#1
Arandel Ludovic, Polay-Espinosa Micaela, Matloka Magdalena, Bazinet Audrey, De Dea Diniz Damily, Naouar Naïra, Rau Frédérique, Jollet Arnaud, Edom-Vovard Frédérique, Mamchaoui Kamel, Tarnopolsky Mark, Puymirat Jack, Battail Christophe, Boland Anne, Deleuze Jean-Francois, Mouly Vincent, Klein F Arnaud, Furling Denis
Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA-aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared to control and DM2 cells...
February 10, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28186492/requirement-of-myomaker-mediated-stem-cell-fusion-for-skeletal-muscle-hypertrophy
#2
Qingnian Goh, Douglas P Millay
Fusion of skeletal muscle stem/progenitor cells is required for proper development and regeneration, however the significance of this process during adult muscle hypertrophy has not been explored. In response to muscle overload after synergist ablation in mice, we show that myomaker, a muscle specific membrane protein essential for myoblast fusion, is activated mainly in muscle progenitors and not myofibers. We rendered muscle progenitors fusion-incompetent through genetic deletion of myomaker in muscle stem cells and observed a complete reduction of overload-induced hypertrophy...
February 10, 2017: ELife
https://www.readbyqxmd.com/read/28168016/deletion-of-the-ste20-like-kinase-slk-in-skeletal-muscle-results-in-a-progressive-myopathy-and-muscle-weakness
#3
Benjamin R Pryce, Khalid N Al-Zahrani, Sébastien Dufresne, Natalya Belkina, Cédrik Labrèche, Genaro Patino-Lopez, Jérôme Frenette, Stephen Shaw, Luc A Sabourin
BACKGROUND: The Ste20-like kinase, SLK, plays an important role in cell proliferation and cytoskeletal remodeling. In fibroblasts, SLK has been shown to respond to FAK/Src signaling and regulate focal adhesion turnover through Paxillin phosphorylation. Full-length SLK has also been shown to be essential for embryonic development. In myoblasts, the overexpression of a dominant negative SLK is sufficient to block myoblast fusion. METHODS: In this study, we crossed the Myf5-Cre mouse model with our conditional SLK knockout model to delete SLK in skeletal muscle...
2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28154884/antibody-mediated-enzyme-replacement-therapy-targeting-both-lysosomal-and-cytoplasmic-glycogen-in-pompe-disease
#4
Haiqing Yi, Tao Sun, Dustin Armstrong, Scott Borneman, Chunyu Yang, Stephanie Austin, Priya S Kishnani, Baodong Sun
: Pompe disease is characterized by accumulation of both lysosomal and cytoplasmic glycogen primarily in skeletal and cardiac muscles. Mannose-6-phosphate receptor-mediated enzyme replacement therapy (ERT) with recombinant human acid α-glucosidase (rhGAA) targets the enzyme to lysosomes and thus is unable to digest cytoplasmic glycogen. Studies have shown that anti-DNA antibody 3E10 penetrates living cells and delivers "cargo" proteins to the cytosol or nucleus via equilibrative nucleoside transporter ENT2...
February 2, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28153048/deletion-of-the-ste20-like-kinase-slk-in-skeletal-muscle-results-in-a-progressive-myopathy-and-muscle-weakness
#5
Benjamin R Pryce, Khalid N Al-Zahrani, Sébastien Dufresne, Natalya Belkina, Cédrik Labrèche, Genaro Patino-Lopez, Jérôme Frenette, Stephen Shaw, Luc A Sabourin
BACKGROUND: The Ste20-like kinase, SLK, plays an important role in cell proliferation and cytoskeletal remodeling. In fibroblasts, SLK has been shown to respond to FAK/Src signaling and regulate focal adhesion turnover through Paxillin phosphorylation. Full-length SLK has also been shown to be essential for embryonic development. In myoblasts, the overexpression of a dominant negative SLK is sufficient to block myoblast fusion. METHODS: In this study, we crossed the Myf5-Cre mouse model with our conditional SLK knockout model to delete SLK in skeletal muscle...
February 2, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28138962/pax3-foxo1-is-essential-for-tumour-initiation-and-maintenance-but-not-recurrence-in-a-human-myoblast-model-of-rhabdomyosarcoma
#6
Puspa R Pandey, Bishwanath Chatterjee, Mary E Olanich, Javed Khan, Markku M Miettinen, Stephen M Hewitt, Frederic G Barr
The PAX3-FOXO1 fusion gene is generated by a 2;13 chromosomal translocation and is a characteristic feature of an aggressive subset of rhabdomyosarcoma (RMS). To dissect the mechanism of oncogene action during RMS tumourigenesis and progression, doxycycline-inducible PAX3-FOXO1 and constitutive MYCN expression constructs were introduced into immortalised human myoblasts. Though myoblasts expressing PAX3-FOXO1 or MYCN alone were not transformed in focus formation assays, combined PAX3-FOXO1 and MYCN expression resulted in transformation...
January 31, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28101909/efficient-transdifferentiation-of-human-dermal-fibroblasts-into-skeletal-muscle
#7
Selwa Mokhtar Boularaoui, Khaled M A Abdel-Raouf, Noaf Salah Ali Alwahab, Megan E Kondash, George A Truskey, Jeremy Choon Meng Teo, Nicolas Christoforou
Skeletal muscle holds significant regenerative potential but is incapable of restoring tissue loss caused due to severe injury, congenital defects, or tumor ablation. Consequently, skeletal muscle models are being developed to study human pathophysiology and regeneration. Their physiological accuracy, however, is hampered by the lack of an easily accessible human cell source that is readily expandable and capable of efficient differentiation. MYOD1, a master gene regulator, induces transdifferentiation of a variety of cell types into skeletal muscle, although inefficiently in human cells...
January 18, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28097017/study-of-myoblast-differentiation-using-multi-dimensional-scaffolds-consisting-of-nano-and-micropatterns
#8
Sung Ho Cha, Hyun Jong Lee, Won-Gun Koh
BACKGROUND: The topographical cue is major influence on skeletal muscle cell culture because the structure is highly organized and consists of long parallel bundles of multinucleated myotubes that are formed by differentiation and fusion of myoblast satellite cells. In this technical report, we fabricated a multiscale scaffold using electrospinning and poly (ethylene glycol) (PEG) hydrogel micropatterns to monitor the cell behaviors on nano- and micro-alignment combined scaffolds with different combinations of angles...
2017: Biomaterials Research
https://www.readbyqxmd.com/read/28062562/keep-your-friends-close-cell-cell-contact-and-skeletal-myogenesis
#9
Robert S Krauss, Giselle A Joseph, Aviva J Goel
Development of skeletal muscle is a multistage process that includes lineage commitment of multipotent progenitor cells, differentiation and fusion of myoblasts into multinucleated myofibers, and maturation of myofibers into distinct types. Lineage-specific transcriptional regulation lies at the core of this process, but myogenesis is also regulated by extracellular cues. Some of these cues are initiated by direct cell-cell contact between muscle precursor cells themselves or between muscle precursors and cells of other lineages...
January 6, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28044437/body-mass-index-change-in-gastrointestinal-cancer-and-chronic-obstructive-pulmonary-disease-is-associated-with-dedicator-of-cytokinesis-1
#10
Merry-Lynn Noelle McDonald, Sungho Won, Manuel Mattheisen, Peter J Castaldi, Michael H Cho, Erica Rutten, Megan Hardin, Wai-Ki Yip, Stephen I Rennard, David A Lomas, Emiel F M Wouters, Alvar Agusti, Richard Casaburi, Christoph P Lange, George O'Connor, Craig P Hersh, Edwin K Silverman
BACKGROUND: There have been a number of candidate gene association studies of cancer cachexia-related traits, but no genome-wide association study (GWAS) has been published to date. Cachexia presents in patients with a number of complex traits, including both cancer and COPD. The objective of the current investigation was to search for a shared genetic aetiology for change in body mass index (ΔBMI) among cancer and COPD by using GWAS data in the Framingham Heart Study. METHODS: A linear mixed effects model accounting for age, sex, and change in smoking status was used to calculate ΔBMI in participants over 40 years of age with three consecutive BMI time points (n = 4162)...
January 2, 2017: Journal of Cachexia, Sarcopenia and Muscle
https://www.readbyqxmd.com/read/27965114/myogenic-differentiation-depends-on-the-interplay-of-grb2-and-n-wasp
#11
Payal Mitra, Thirumaran Thanabalu
Myogenesis requires a well-coordinated withdrawal from cell cycle, morphological changes and cell fusion mediated by actin cytoskeleton. Grb2 is an adaptor protein whose central SH2 domain binds to phosphorylated tyrosine residues of activated receptors and activates intracellular signaling pathway, while its N-terminal and C-terminal SH3 domains bind to proline rich proteins such as N-WASP (Neural-Wiskott Aldrich Syndrome Protein). We found that the expression of Grb2 was increased at the beginning of differentiation and remained constant during differentiation in C2C12 myoblasts...
December 10, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27964750/laminin-521-maintains-differentiation-potential-of-mouse-and-human-satellite-cell-derived-myoblasts-during-long-term-culture-expansion
#12
Christopher M Penton, Vasudeo Badarinarayana, Joy Prisco, Elaine Powers, Mark Pincus, Ronald E Allen, Paul R August
BACKGROUND: Large-scale expansion of myogenic progenitors is necessary to support the development of high-throughput cellular assays in vitro and to advance genetic engineering approaches necessary to develop cellular therapies for rare muscle diseases. However, optimization has not been performed in order to maintain the differentiation capacity of myogenic cells undergoing long-term cell culture. Multiple extracellular matrices have been utilized for myogenic cell studies, but it remains unclear how different matrices influence long-term myogenic activity in culture...
December 13, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27938324/analysis-and-quantification-of-in-vitro-myoblast-fusion-using-the-ladd-multiple-stain
#13
Rhys McColl, Mthokozisi Nkosi, Celia Snyman, Carola Niesler
Myoblast fusion, which is essential for muscle development, regeneration, and repair, can be assessed in vitro via the calculation of a fusion index. Traditionally, this requires use of either immunocytochemistry or fluorescently-labeled cytoskeletal staining, followed by microscopy and laborious analysis. The expense and time-consuming nature of the optimization and application of antibody-based techniques such as immunocytochemistry, as well as the need for specialized analytical equipment such as fluorescence microscopes, presents a barrier to the routine analysis of this crucial step during terminal differentiation...
December 1, 2016: BioTechniques
https://www.readbyqxmd.com/read/27920252/group-i-paks-promote-skeletal-myoblast-differentiation-in-vivo-and-in-vitro
#14
Giselle A Joseph, Min Lu, Maria Radu, Jennifer K Lee, Steven J Burden, Jonathan Chernoff, Robert S Krauss
Skeletal myogenesis is regulated by signal transduction, but the factors and mechanisms involved are not well understood. The group I Paks Pak1 and Pak2 are related protein kinases and direct effectors of Cdc42 and Rac1. Group I Paks are ubiquitously expressed and specifically required for myoblast fusion in Drosophila We report that both Pak1 and Pak2 are activated during mammalian myoblast differentiation. One pathway of activation is initiated by N-cadherin ligation and involves the cadherin coreceptor Cdo with its downstream effector, Cdc42...
February 15, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27911334/matrix-metalloproteinases-and-tissue-inhibitor-of-metalloproteinases-in%C3%A2-inflammation-and-fibrosis-of-skeletal-muscles
#15
Hala S Alameddine, Jennifer E Morgan
In skeletal muscles, levels and activity of Matrix MetalloProteinases (MMPs) and Tissue Inhibitors of MetalloProteinases (TIMPs) have been involved in myoblast migration, fusion and various physiological and pathological remodeling situations including neuromuscular diseases. This has opened perspectives for the use of MMPs' overexpression to improve the efficiency of cell therapy in muscular dystrophies and resolve fibrosis. Alternatively, inhibition of individual MMPs in animal models of muscular dystrophies has provided evidence of beneficial, dual or adverse effects on muscle morphology or function...
November 29, 2016: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/27906069/the-beneficial-role-of-proteolysis-in-skeletal-muscle-growth-and-stress-adaptation
#16
REVIEW
Ryan A V Bell, Mohammad Al-Khalaf, Lynn A Megeney
Muscle atrophy derived from excessive proteolysis is a hallmark of numerous disease conditions. Accordingly, the negative consequences of skeletal muscle protein breakdown often overshadow the critical nature of proteolytic systems in maintaining normal cellular function. Here, we discuss the major cellular proteolysis machinery-the ubiquitin/proteosome system, the autophagy/lysosomal system, and caspase-mediated protein cleavage-and the critical role of these protein machines in establishing and preserving muscle health...
April 6, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27836432/macrophage-ppar%C3%AE-a-lipid-activated-transcription-factor-controls-the-growth-factor-gdf3-and-skeletal-muscle-regeneration
#17
Tamas Varga, Rémi Mounier, Andreas Patsalos, Péter Gogolák, Matthew Peloquin, Attila Horvath, Attila Pap, Bence Daniel, Gergely Nagy, Eva Pintye, Szilárd Poliska, Sylvain Cuvellier, Sabrina Ben Larbi, Brian E Sansbury, Matthew Spite, Chester W Brown, Bénédicte Chazaud, Laszlo Nagy
Tissue regeneration requires inflammatory and reparatory activity of macrophages. Macrophages detect and eliminate the damaged tissue and subsequently promote regeneration. This dichotomy requires the switch of effector functions of macrophages coordinated with other cell types inside the injured tissue. The gene regulatory events supporting the sensory and effector functions of macrophages involved in tissue repair are not well understood. Here we show that the lipid activated transcription factor, PPARγ, is required for proper skeletal muscle regeneration, acting in repair macrophages...
November 15, 2016: Immunity
https://www.readbyqxmd.com/read/27825154/growth-factors-for-skeletal-muscle-tissue-engineering
#18
Brian C Syverud, Keith W VanDusen, Lisa M Larkin
Tissue-engineered skeletal muscle holds promise as a source of graft tissue for repair of volumetric muscle loss and as a model system for pharmaceutical testing. To reach this potential, engineered tissues must advance past the neonatal phenotype that characterizes the current state of the art. In this review, we describe native skeletal muscle development and identify important growth factors controlling this process. By comparing in vivo myogenesis to in vitro satellite cell cultures and tissue engineering approaches, several key similarities and differences that may potentially advance tissue-engineered skeletal muscle were identified...
2016: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/27825107/in-vivo-myomaker-mediated-heterologous-fusion-and-nuclear-reprogramming
#19
Yasuyuki Mitani, Ronald J Vagnozzi, Douglas P Millay
Knowledge regarding cellular fusion and nuclear reprogramming may aid in cell therapy strategies for skeletal muscle diseases. An issue with cell therapy approaches to restore dystrophin expression in muscular dystrophy is obtaining a sufficient quantity of cells that normally fuse with muscle. Here we conferred fusogenic activity without transdifferentiation to multiple non-muscle cell types and tested dystrophin restoration in mouse models of muscular dystrophy. We previously demonstrated that myomaker, a skeletal muscle-specific transmembrane protein necessary for myoblast fusion, is sufficient to fuse 10T 1/2 fibroblasts to myoblasts in vitro...
January 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27802164/nuclear-alignment-in-myotubes-requires-centrosome-proteins-recruited-by-nesprin-1
#20
Aude Espigat-Georger, Vyacheslav Dyachuk, Cécile Chemin, Laurent Emorine, Andreas Merdes
Myotubes are syncytial cells generated by fusion of myoblasts. Among the numerous nuclei in myotubes of skeletal muscle fibres, the majority are equidistantly positioned at the periphery, except for clusters of multiple nuclei underneath the motor endplate. The correct positioning of nuclei is thought to be important for muscle function and requires nesprin-1 (also known as SYNE1), a protein of the nuclear envelope. Consistent with this, mice lacking functional nesprin-1 show defective nuclear positioning and present aspects of Emery-Dreifuss muscular dystrophy...
November 15, 2016: Journal of Cell Science
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