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https://www.readbyqxmd.com/read/28808339/direct-reprogramming-of-fibroblasts-into-skeletal-muscle-progenitor-cells-by-transcription-factors-enriched-in-undifferentiated-subpopulation-of-satellite-cells
#1
Naoki Ito, Isao Kii, Noriaki Shimizu, Hirotoshi Tanaka, Takeda Shin'ichi
Satellite cells comprise a functionally heterogeneous population of stem cells in skeletal muscle. Separation of an undifferentiated subpopulation and elucidation of its molecular background are necessary to identify the reprogramming factors to induce skeletal muscle progenitor cells. In this study, we found that intracellular esterase activity distinguishes a subpopulation of cultured satellite cells with high stemness using esterase-sensitive cell staining reagent, calcein-AM. Gene expression analysis of this subpopulation revealed that defined combinations of transcription factors (Pax3, Mef2b, and Pitx1 or Pax7, Mef2b, and Pitx1 in embryonic fibroblasts, and Pax7, Mef2b and MyoD in adult fibroblasts) reprogrammed fibroblasts into skeletal muscle progenitor cells...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28790171/the-ror1-receptor-tyrosine-kinase-plays-a-critical-role-in-regulating-satellite-cell-proliferation-during-regeneration-of-injured-muscle
#2
Koki Kamizaki, Ryosuke Doi, Makoto Hayashi, Takeshi Saji, Motoi Kanagawa, Tatsushi Toda, So-Ichiro Fukada, Hsin-Yi Henry Ho, Michael Eldon Greenberg, Mitsuharu Endo, Yasuhiro Minami
The Ror family receptor tyrosine kinases, Ror1 and Ror2 play important roles in regulating developmental morphogenesis and tissue- and organogenesis, but their roles in tissue regeneration in adult animals remains largely unknown. In this study, we examined the expression and function of Ror1 and Ror2 during skeletal muscle regeneration. Using an in vivo skeletal muscle injury model, we show that expression of Ror1 and Ror2 in skeletal muscles is induced transiently by the inflammatory cytokines, TNF-α and IL-1β, after injury, and that inhibition of TNF-α and IL-1β by neutralizing antibodies suppresses expression of Ror1 and Ror2 in injured muscles...
August 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28756524/muscle-satellite-cells-are-functionally-impaired-in-myasthenia-gravis-consequences-on-muscle-regeneration
#3
Mohamed Attia, Marie Maurer, Marieke Robinet, Fabien Le Grand, Elie Fadel, Rozen Le Panse, Gillian Butler-Browne, Sonia Berrih-Aknin
Myasthenia gravis (MG) is a neuromuscular disease caused in most cases by anti-acetyl-choline receptor (AChR) autoantibodies that impair neuromuscular signal transmission and affect skeletal muscle homeostasis. Myogenesis is carried out by muscle stem cells called satellite cells (SCs). However, myogenesis in MG had never been explored. The aim of this study was to characterise the functional properties of myasthenic SCs as well as their abilities in muscle regeneration. SCs were isolated from muscle biopsies of MG patients and age-matched controls...
July 29, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28740214/compensatory-anabolic-signaling-in-the-sarcopenia-of-experimental-chronic-arthritis
#4
Robert D Little, Iván Prieto-Potin, Sandra Pérez-Baos, Amanda Villalvilla, Paula Gratal, Flavia Cicuttini, Raquel Largo, Gabriel Herrero-Beaumont
Inflammatory activity in rheumatoid arthritis may alter the regulation of muscle mass leading to a secondary sarcopenia, commonly termed rheumatoid cachexia (RC). We characterized alterations to muscle structure and various pro-inflammatory, catabolic and regenerative markers in an animal model of RC. Antigen induced arthritis (AiA) was performed in 20 male adult rabbits. AiA animals exhibited significantly less weight gain, a markedly elevated serum C-reactive protein (CRP), lighter muscles with shorter cross-sectional diameter and increased myonuclei when compared to controls...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28736900/depletion-of-pax7-satellite-cells-does-not-affect-diaphragm-adaptations-to-running-in-young-or-aged-mice
#5
Kevin A Murach, Amy L Confides, Angel Ho, Janna R Jackson, Lina S Ghazala, Charlotte A Peterson, Esther E Dupont-Versteegden
Satellite cell contribution to un-stressed diaphragm is higher compared to hind limb muscles, which is likely attributable to constant activation of this muscle to drive ventilation. Whether satellite cell depletion negatively impacts diaphragm quantitative and qualitative characteristics under stressed conditions in young and aged mice is unknown. We therefore challenged the diaphragm with prolonged running activity in the presence and absence of Pax7+ satellite cells in young and aged mice using an inducible Pax7(CreER) -R26R(DTA) model...
July 24, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28735515/determination-of-cell-fate-in-skeletal-muscle-following-bmp-gene-transfer-by-in-vivo-electroporation
#6
Mariko Kawai, Yu-Ki Ohmori, Mai Nishino, Masayo Yoshida, Kaori Tabata, Do-Saku Hirota, Ayako Ryu-Mon, Hiromitsu Yamamoto, Junya Sonobe, Yo-Hei Kataoka, Noriko Shiotsu, Mika Ikegame, Hiroki Maruyama, Toshio Yamamoto, Kazuhisa Bessho, Kiyoshi Ohura
We previously developed a novel method for gene transfer, which combined a non-viral gene expression vector with transcutaneous in vivo electroporation. We applied this method to transfer the bone morphogenetic protein (BMP) gene and induce ectopic bone formation in rat skeletal muscles. At present, it remains unclear which types of cells can differentiate into osteogenic cells after BMP gene transfer by in vivo electroporation. Two types of stem cells in skeletal muscle can differentiate into osteogenic cells: muscle-derived stem cells, and bone marrow-derived stem cells in the blood...
May 5, 2017: European Journal of Histochemistry: EJH
https://www.readbyqxmd.com/read/28732241/generation-of-skeletal-myogenic-progenitors-from-human-pluripotent-stem-cells-using-non-viral-delivery-of-minicircle-dna
#7
Jaemin Kim, Vanessa K P Oliveira, Ami Yamamoto, Rita C R Perlingeiro
Currently, the most efficient and promising approach for generating large numbers of engraftable human skeletal myogenic progenitors from pluripotent stem cells requires the conditional in vitro overexpression of PAX7 using lentiviral vectors. Because a non-integrating approach would be preferable to eliminate or minimize the risk associated with random genomic integration, here we investigate whether transient expression of PAX7 using minicircle DNA would enable the generation of functional pluripotent stem cell-derived myogenic progenitors, equivalent to those generated by lentivirus...
July 12, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28721121/does-the-injection-of-platelet-rich-plasma-induce-changes-in-the-gene-expression-and-morphology-of-intact-thoroughbred-skeletal-muscle
#8
Kentaro Fukuda, Hirofumi Miyata, Atsutoshi Kuwano, Taisuke Kuroda, Norihisa Tamura, Yasumitsu Kotoyori, Yoshinori Kasashima
Platelet-rich plasma (PRP) therapy is promising for treating skeletal muscle injuries in human athletes by promoting muscle regeneration. It might also be useful for treating muscle injuries in equine athletes. In the present study, muscle regeneration induced by injection of PRP into intact muscle of Thoroughbred was investigated. Autologous PRP and saline were injected twice into intact left and right gluteus medius muscles of seven clinically healthy Thoroughbreds. Muscle samples were collected from the injection sites by needle biopsy at 2 and 7 days after PRP injection...
2017: Journal of Equine Science
https://www.readbyqxmd.com/read/28714082/in-situ-macrophage-phenotypic-transition-is-affected-by-altered-cellular-composition-prior-to-acute-sterile-muscle-injury
#9
Andreas Patsalos, Attila Pap, Tamas Varga, Gyorgy Trencsenyi, Gerardo Alvarado Contreras, Ildiko Garai, Zoltan Papp, Balazs Dezso, Eva Pintye, Laszlo Nagy
Skeletal muscle regeneration is a complex interplay between various cell types including invading macrophages. Their recruitment to damaged tissues upon acute sterile injuries is necessary for necrotic debris clearance and for coordination of tissue regeneration. This highly dynamic process is characterized by an in-situ transition of infiltrating monocytes from an inflammatory (Ly6C(high) ) to a repair (Ly6C(low) ) macrophage phenotype. The importance of the macrophage phenotypic shift and the cross-talk of the local muscle tissue with the infiltrating macrophages during tissue regeneration upon injury are not fully understood and their study lacks adequate methodology...
July 17, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28700649/autophagy-mediates-cell-cycle-response-by-regulating-nucleocytoplasmic-transport-of-pax6-in-limbal-stem-cells-under-ultraviolet-a-stress
#10
Maria Laggner, Andreas Pollreisz, Gerald Schmidinger, Ursula Schmidt-Erfurth, Ying-Ting Chen
Limbal stem cells (LSC) account for homeostasis and regeneration of corneal epithelium. Solar ultraviolet A (UVA) is the major source causing oxidative damage in the ocular surface. Autophagy, a lysosomal degradation mechanism, is essential for physiologic function and stress defense of stem cells. PAX6, a master transcription factor governing corneal homeostasis by regulating cell cycle and cell fate of LSC, responds to oxidative stress by nucleocytoplasmic shuttling. Impaired autophagy and deregulated PAX6 have been reported in oxidative stress-related ocular surface disorders...
2017: PloS One
https://www.readbyqxmd.com/read/28693603/differential-requirement-for-satellite-cells-during-overload-induced-muscle-hypertrophy-in-growing-versus-mature-mice
#11
Kevin A Murach, Sarah H White, Yuan Wen, Angel Ho, Esther E Dupont-Versteegden, John J McCarthy, Charlotte A Peterson
BACKGROUND: Pax7+ satellite cells are required for skeletal muscle fiber growth during post-natal development in mice. Satellite cell-mediated myonuclear accretion also appears to persist into early adulthood. Given the important role of satellite cells during muscle development, we hypothesized that the necessity of satellite cells for adaptation to an imposed hypertrophic stimulus depends on maturational age. METHODS: Pax7(CreER)-R26R(DTA) mice were treated for 5 days with vehicle (satellite cell-replete, SC+) or tamoxifen (satellite cell-depleted, SC-) at 2 months (young) and 4 months (mature) of age...
July 10, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28689354/functional-and-molecular-characterization-of-a-novel-traumatic-peripheral-nerve-muscle-injury-model
#12
Renate Wanner, Manuel Gey, Alireza Abaei, Daniela Warnecke, Luisa de Roy, Lutz Dürselen, Volker Rasche, Bernd Knöll
Traumatic injuries to human peripheral nerves are frequently associated with damage to nerve surrounding tissues including muscles and blood vessels. Currently, most rodent models of peripheral nerve injuries (e.g., facial or sciatic nerve) employ surgical nerve transection with scissors or scalpels. However, such an isolated surgical nerve injury only mildly damages neighboring tissues and weakly activates an immune response. In order to provide a rodent nerve injury model accounting for such nerve-associated tissue damage and immune cell activation, we developed a drop tower-based facial nerve trauma model in mice...
July 8, 2017: Neuromolecular Medicine
https://www.readbyqxmd.com/read/28676130/skeletal-muscle-derived-interstitial-progenitor-cells-pics-display-stem-cell-properties-being-clonogenic-self-renewing-and-multi-potent-in-vitro-and-in-vivo
#13
Beverley J Cottle, Fiona C Lewis, Victoria Shone, Georgina M Ellison-Hughes
BACKGROUND: The development of cellular therapies to treat muscle wastage with disease or age is paramount. Resident muscle satellite cells are not currently regarded as a viable cell source due to their limited migration and growth capability ex vivo. This study investigated the potential of muscle-derived PW1(+)/Pax7(-) interstitial progenitor cells (PICs) as a source of tissue-specific stem/progenitor cells with stem cell properties and multipotency. METHODS: Sca-1(+)/PW1(+) PICs were identified on tissue sections from hind limb muscle of 21-day-old mice, isolated by magnetic-activated cell sorting (MACS) technology and their phenotype and characteristics assessed over time in culture...
July 4, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28662356/a-population-based-study-of-effects-of-genetic-loci-on-orofacial-clefts
#14
L M Moreno Uribe, T Fomina, R G Munger, P A Romitti, M M Jenkins, H K Gjessing, M Gjerdevik, K Christensen, A J Wilcox, J C Murray, R T Lie, G L Wehby
Prior genome-wide association studies for oral clefts have focused on clinic-based samples with unclear generalizability. Prior samples were also small for investigating effects by cleft type and exclusively studied isolated clefts (those occurring without other birth defects). We estimated the effects of 17 top loci on cleft types in both isolated and nonisolated cases in the largest consortium to date of European-descent population-based studies. Our analytic approach focused on a mother-child dyad case-control design, but it also allowed analyzing mother-only or child-only genotypes to maximize power...
June 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28658631/pax7-targets-cd54-integrin-%C3%AE-9%C3%AE-1-and-sdc2-allow-isolation-of-human-esc-ipsc-derived-myogenic-progenitors
#15
Alessandro Magli, Tania Incitti, James Kiley, Scott A Swanson, Radbod Darabi, Fabrizio Rinaldi, Sridhar Selvaraj, Ami Yamamoto, Jakub Tolar, Ce Yuan, Ron Stewart, James A Thomson, Rita C R Perlingeiro
Pluripotent stem (PS)-cell-derived cell types hold promise for treating degenerative diseases. However, PS cell differentiation is intrinsically heterogeneous; therefore, clinical translation requires the development of practical methods for isolating progenitors from unwanted and potentially teratogenic cells. Muscle-regenerating progenitors can be derived through transient PAX7 expression. To better understand the biology, and to discover potential markers for these cells, here we investigate PAX7 genomic targets and transcriptional changes in human cells undergoing PAX7-mediated myogenic commitment...
June 27, 2017: Cell Reports
https://www.readbyqxmd.com/read/28643791/ewsr1-fusion-proteins-mediate-pax7-expression-in-ewing-sarcoma
#16
Gregory W Charville, Wei-Lien Wang, Davis R Ingram, Angshumoy Roy, Dafydd Thomas, Rajiv M Patel, Jason L Hornick, Matt van de Rijn, Alexander J Lazar
PAX7 is a paired-box transcription factor that is required for the developmental specification of adult skeletal muscle progenitors in mice. We previously demonstrated PAX7 expression as a marker of skeletal muscle differentiation in rhabdomyosarcoma. Here, using analyses of published whole-genome gene expression microarray data, we identify PAX7 as a gene with significantly increased expression in Ewing sarcoma in comparison to CIC-DUX4 round cell sarcoma. Analysis of PAX7 in a large cohort of 103 Ewing sarcoma cases by immunohistochemistry revealed expression in 99...
June 23, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28637492/expression-patterns-of-fshd-causing-dux4-and-myogenic-transcription-factors-pax3-and-pax7-are-spatially-distinct-in-differentiating-human-stem-cell-cultures
#17
Premi Haynes, Kelly Kernan, Suk-Lin Zhou, Daniel G Miller
BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is most commonly inherited in an autosomal dominant pattern and caused by the abnormal expression of DUX4 in skeletal muscle. The DUX4 transcription factor has DNA binding domains similar to several paired class homeotic transcription factors, but only myogenic factors PAX3 and PAX7 rescue cell viability when co-expressed with DUX4 in mouse myoblasts. This observation suggests competition for DNA binding sites in satellite cells might limit muscle repair and may be one aspect of DUX4-associated myotoxicity...
June 21, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28625870/pax3-and-pax7-mediated-dbx1-regulation-orchestrates-the-patterning-of-intermediate-spinal-interneurons
#18
Chris Gard, Gloria Gonzalez Curto, Youcef El-Mokhtar Frarma, Elodie Chollet, Nathalie Duval, Valentine Auzié, Frédéric Auradé, Lisa Vigier, Frédéric Relaix, Alessandra Pierani, Frédéric Causeret, Vanessa Ribes
Transcription factors are key orchestrators of the emergence of neuronal diversity within the developing spinal cord. As such, the two paralogous proteins Pax3 and Pax7 regulate the specification of progenitor cells within the intermediate neural tube, by defining a neat segregation between those fated to form motor circuits and those involved in the integration of sensory inputs. To attain insights into the molecular means by which they control this process, we have performed detailed phenotypic analyses of the intermediate spinal interneurons (IN), namely the dI6, V0D, V0VCG and V1 populations in compound null mutants for Pax3 and Pax7...
June 16, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28615691/human-myogenic-reserve-cells-are-quiescent-stem-cells-that-contribute-to-muscle-regeneration-after-intramuscular-transplantation-in-immunodeficient-mice
#19
Thomas Laumonier, Flavien Bermont, Pierre Hoffmeyer, Vincent Kindler, Jacques Menetrey
Satellite cells, localized within muscles in vivo, are Pax7(+) muscle stem cells supporting skeletal muscle growth and regeneration. Unfortunately, their amplification in vitro, required for their therapeutic use, is associated with reduced regenerative potential. In the present study, we investigated if human myogenic reserve cells (MRC) obtained in vitro, represented a reliable cell source for muscle repair. For this purpose, primary human myoblasts were freshly isolated and expanded. After 2 days of differentiation, 62 ± 2...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28607396/cxcl12-and-osteopontin-from-bone-marrow-derived-mesenchymal-stromal-cells-improve-muscle-regeneration
#20
Yasushi Maeda, Yasuhiro Yonemochi, Yuki Nakajyo, Hideaki Hidaka, Tokunori Ikeda, Yukio Ando
Muscle satellite cells are essential for muscle regeneration. However, efficient regeneration does not occur without muscle-resident mesenchymal progenitor cells. We show here that bone marrow-derived mesenchymal stromal cells (Bm-MSCs) also facilitate muscle regeneration in Duchenne muscular dystrophy (DMD) model mice. Bm-MSCs transplanted into peritoneal cavities of DMD model mice with severe muscle degeneration strongly suppressed dystrophic pathology and improved death-related symptoms, which resulted in dramatic lifespan extension...
June 12, 2017: Scientific Reports
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