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https://www.readbyqxmd.com/read/28643791/ewsr1-fusion-proteins-mediate-pax7-expression-in-ewing-sarcoma
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28600779/the-landscape-of-genetic-diseases-in-saudi-arabia-based-on-the-first-1000-diagnostic-panels-and-exomes
#6
Dorota Monies, Mohamed Abouelhoda, Moeenaldeen AlSayed, Zuhair Alhassnan, Maha Alotaibi, Husam Kayyali, Mohammed Al-Owain, Ayaz Shah, Zuhair Rahbeeni, Mohammad A Al-Muhaizea, Hamad I Alzaidan, Edward Cupler, Saeed Bohlega, Eissa Faqeih, Maha Faden, Banan Alyounes, Dyala Jaroudi, Ewa Goljan, Hadeel Elbardisy, Asma Akilan, Renad Albar, Hesham Aldhalaan, Shamshad Gulab, Aziza Chedrawi, Bandar K Al Saud, Wesam Kurdi, Nawal Makhseed, Tahani Alqasim, Heba Y El Khashab, Hamoud Al-Mousa, Amal Alhashem, Imaduddin Kanaan, Talal Algoufi, Khalid Alsaleem, Talal A Basha, Fathiya Al-Murshedi, Sameena Khan, Adila Al-Kindy, Maha Alnemer, Sami Al-Hajjar, Suad Alyamani, Hasan Aldhekri, Ali Al-Mehaidib, Rand Arnaout, Omar Dabbagh, Mohammad Shagrani, Dieter Broering, Maha Tulbah, Amal Alqassmi, Maisoon Almugbel, Mohammed AlQuaiz, Abdulaziz Alsaman, Khalid Al-Thihli, Raashda A Sulaiman, Wajeeh Al-Dekhail, Abeer Alsaegh, Fahad A Bashiri, Alya Qari, Suzan Alhomadi, Hisham Alkuraya, Mohammed Alsebayel, Muddathir H Hamad, Laszlo Szonyi, Faisal Abaalkhail, Sulaiman M Al-Mayouf, Hamad Almojalli, Khalid S Alqadi, Hussien Elsiesy, Taghreed M Shuaib, Mohammed Zain Seidahmed, Ibraheem Abosoudah, Hana Akleh, Abdulaziz AlGhonaium, Turki M Alkharfy, Fuad Al Mutairi, Wafa Eyaid, Abdullah Alshanbary, Farrukh R Sheikh, Fahad I Alsohaibani, Abdullah Alsonbul, Saeed Al Tala, Soher Balkhy, Randa Bassiouni, Ahmed S Alenizi, Maged H Hussein, Saeed Hassan, Mohamed Khalil, Brahim Tabarki, Saad Alshahwan, Amira Oshi, Yasser Sabr, Saad Alsaadoun, Mustafa A Salih, Sarar Mohamed, Habiba Sultana, Abdullah Tamim, Moayad El-Haj, Saif Alshahrani, Dalal K Bubshait, Majid Alfadhel, Tariq Faquih, Mohamed El-Kalioby, Shazia Subhani, Zeeshan Shah, Nabil Moghrabi, Brian F Meyer, Fowzan S Alkuraya
In this study, we report the experience of the only reference clinical next-generation sequencing lab in Saudi Arabia with the first 1000 families who span a wide-range of suspected Mendelian phenotypes. A total of 1019 tests were performed in the period of March 2016-December 2016 comprising 972 solo (index only), 14 duo (parents or affected siblings only), and 33 trio (index and parents). Multigene panels accounted for 672 tests, while whole exome sequencing (WES) represented the remaining 347 tests. Pathogenic or likely pathogenic variants that explain the clinical indications were identified in 34% (27% in panels and 43% in exomes), spanning 279 genes and including 165 novel variants...
June 9, 2017: Human Genetics
https://www.readbyqxmd.com/read/28597942/copy-number-alterations-determined-by-single-nucleotide-polymorphism-array-testing-in-the-clinical-laboratory-are-indicative-of-gene-fusions-in-pediatric-cancer-patients
#7
Tracy M Busse, Jacquelyn J Roth, Donna Wilmoth, Luanne Wainwright, Laura Tooke, Jaclyn A Biegel
Gene fusions resulting from structural rearrangements are an established mechanism of tumorigenesis in pediatric cancer. In this clinical cohort, 1,350 single nucleotide polymorphism (SNP)-based chromosomal microarrays from 1,211 pediatric cancer patients were evaluated for copy number alterations (CNAs) associated with gene fusions. Karyotype or fluorescence in situ hybridization studies were performed in 42% of the patients. Ten percent of the bone marrow or solid tumor specimens had SNP array-associated CNAs suggestive of a gene fusion...
June 9, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28596299/postexercise-essential-amino-acid-supplementation-amplifies-skeletal-muscle-satellite-cell-proliferation-in-older-men-24%C3%A2-hours-postexercise
#8
Paul T Reidy, Christopher S Fry, Jared M Dickinson, Micah J Drummond, Blake B Rasmussen
Aged skeletal muscle has an attenuated and delayed ability to proliferate satellite cells in response to resistance exercise. The mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway is a focal point for cell growth, however, the effect of postexercise mTORC1 activation on human skeletal muscle satellite cell (SC) proliferation is unknown. To test the proliferative capacity of skeletal muscle SC in aging muscle to a potent mTORC1 activator (i.e., EAA; essential amino acids) we recruited older (~72y) men to conduct leg resistance exercise (8setsx10reps) without (-EAA; n = 8) and with (+EAA: n = 11) ingestion of 10 g of EAA 1 h postexercise...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28589555/common-and-distinctive-functions-of-the-hippo-effectors-taz-and-yap-in-skeletal-muscle-stem-cell-function
#9
Congshan Sun, Vanessa De Mello, Abdalla Mohamed, Huascar P Ortuste Quiroga, Amaya Garcia-Munoz, Abdullah Al Bloshi, Annie M Tremblay, Alexander von Kriegsheim, Elaina Collie-Duguid, Neil Vargesson, David Matallanas, Henning Wackerhage, Peter S Zammit
Hippo pathway downstream effectors Yap and Taz play key roles in cell proliferation and regeneration, regulating gene expression especially via Tead transcription factors. To investigate their role in skeletal muscle stem cells, we analysed Taz in vivo and ex vivo in comparison to Yap. siRNA knockdown or retroviral-mediated expression of wildtype human or constitutively active TAZ mutants in satellite cells showed that TAZ promoted proliferation, a function shared with YAP. However, at later stages of myogenesis, TAZ also enhanced myogenic differentiation of myoblasts, whereas YAP inhibits such differentiation...
June 7, 2017: Stem Cells
https://www.readbyqxmd.com/read/28576418/a-methyl-balanced-diet-prevents-crf-induced-prenatal-stress-triggered-predisposition-to-binge-eating-like-phenotype
#10
Mariana Schroeder, Mira Jakovcevski, Tamar Polacheck, Maya Lebow, Yonat Drori, Mareen Engel, Shifra Ben-Dor, Alon Chen
Binge eating (BE) is a common aberrant form of eating behavior, characterized by overconsumption of food in a brief period of time. Recurrent episodes of BE constitute the BE disorder, which mostly affects females and is associated with early-life adversities. Here, we show that corticotropin releasing factor (CRF)-induced prenatal stress (PNS) in late gestation predisposes female offspring to BE-like behavior that coincides with hypomethylation of hypothalamic miR-1a and downstream dysregulation of the melanocortin system through Pax7/Pax3...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28574407/muscular-response-to-the-first-three-months-of-deflazacort-treatment-in-boys-with-duchenne-muscular-dystrophy
#11
L Jensen, S J Petersson, N O Illum, H C Laugaard-Jacobsen, T Thelle, L H Jørgensen, H D Schrøder
OBJECTIVE: Duchenne muscular dystrophy (DMD) patients are often treated with glucocorticoids; yet their precise molecular action remains unknown. METHODS: We investigated muscle biopsies from nine boys with DMD (aged: 7,6±2,8 yrs.) collected before and after three months of deflazacort treatment and compared them to eight healthy boys (aged: 5,3±2,4 yrs.). mRNA transcripts involved in activation of satellite cells, myogenesis, regeneration, adipogenesis, muscle growth and tissue inflammation were assessed...
June 1, 2017: Journal of Musculoskeletal & Neuronal Interactions
https://www.readbyqxmd.com/read/28572500/neuromuscular-electrical-stimulation-improves-skeletal-muscle-regeneration-through-satellite-cell-fusion-with-myofibers-in-healthy-elderly-subjects
#12
Ester Sara Di Filippo, Rosa Mancinelli, Mariangela Marrone, Christian Doria, Vittore Verratti, Luana Toniolo, Josè Luiz Dantas, Stefania Fulle, Tiziana Pietrangelo
The aim was to determine whether neuromuscular electrical stimulation (NMES) affects skeletal muscle regeneration through a reduction of oxidative status in satellite cells of healthy elderly subjects. Satellite cells from the Vastus lateralis skeletal muscle of 12 healthy elderly subjects before and after 8 weeks of NMES were allowed to proliferate to provide myogenic populations of adult stem cells (myogenic precursor cells; MPCs). These MPCs were then investigated in terms of their proliferation, their basal cytoplasmic free Ca(2+) concentrations, and their expression of myogenic regulatory factors (PAX3, PAX7, MYF5, MYOD, MYOG) and microRNAs (miR-1, miR-133a/b, miR-206)...
June 1, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28542722/a-homozygous-potentially-pathogenic-variant-in-the-paxbp1-gene-in-a-large-family-with-global-developmental-delay-and-myopathic-hypotonia
#13
Essa Alharby, Alia M Albalawi, Abdul Nasir, Sabri A Alhijji, Amer Mahmood, Khushnooda Ramzan, Firoz Abdusamad, Abdulkarim Aljohani, Osama Abdelsalam, Amr Eldardear, Sulman Basit
PAX binding protein 1 (PAXBP1) is an adaptor protein linking the transcription factor PAX3 and PAX7 to the histone methylation machinery. PAXBP1 is a nuclear protein and its high expression is known in brain cerebellar hemisphere and cerebellum. Moreover, it is also found in abundance in muscle precursor cells that are involved in myogenesis and skeletal muscles formation. Whole genome SNP genotyping and exome sequencing in a family with distinct syndrome of global developmental delay and hypotonia mapped the disease locus to the chromosome 21q22...
May 19, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28539819/dexamethasone-treatment-at-the-myoblast-stage-enhanced-c2c12-myocyte-differentiation
#14
Der-Sheng Han, Wei-Shiung Yang, Tung-Wei Kao
Background: Glucocorticoids induce skeletal muscle atrophy in many clinical situations; however, their hypertrophic and pro-differentiation effects on myotubes have rarely been reported. We hypothesized that dexamethasone (DEX) has a dual effect on muscle differentiation, and aimed to develop a new differentiation protocol for C2C12 cell line. Methods: Dose- and time-dependent effect of DEX on C2C12 myoblast cell line was analyzed at myoblast and myotube stage, respectively. The level of differentiation was determined by myh1, pax7, atrogin-1, and myostatin mRNA expression and fusion index...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28535373/a-molecular-switch-regulating-cell-fate-choice-between-muscle-progenitor-cells-and-brown-adipocytes
#15
Yitai An, Gang Wang, Yarui Diao, Yanyang Long, Xinrong Fu, Mingxi Weng, Liang Zhou, Kun Sun, Tom H Cheung, Nancy Y Ip, Hao Sun, Huating Wang, Zhenguo Wu
During mouse embryo development, both muscle progenitor cells (MPCs) and brown adipocytes (BAs) are known to derive from the same Pax7(+)/Myf5(+) progenitor cells. However, the underlying mechanisms for the cell fate control remain unclear. In Pax7-null MPCs from young mice, several BA-specific genes, including Prdm16 and Ucp1 and many other adipocyte-related genes, were upregulated with a concomitant reduction of Myod and Myf5, two muscle lineage-determining genes. This suggests a cell fate switch from MPC to BA...
May 22, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28528701/expansion-and-purification-are-critical-for-the-therapeutic-application-of-pluripotent-stem-cell-derived-myogenic-progenitors
#16
Jaemin Kim, Alessandro Magli, Sunny S K Chan, Vanessa K P Oliveira, Jianbo Wu, Radbod Darabi, Michael Kyba, Rita C R Perlingeiro
Recent reports have documented the differentiation of human pluripotent stem cells toward the skeletal myogenic lineage using transgene- and cell purification-free approaches. Although these protocols generate myocytes, they have not demonstrated scalability, safety, and in vivo engraftment, which are key aspects for their future clinical application. Here we recapitulate one prominent protocol, and show that it gives rise to a heterogeneous cell population containing myocytes and other cell types. Upon transplantation, the majority of human donor cells could not contribute to myofiber formation...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28512922/effect-of-chemical-immobilization-of-sdf-1%C3%AE-into-muscle-derived-scaffolds-on-angiogenesis-and-muscle-progenitor-recruitment
#17
Sareh Rajabi-Zeleti, Sasan Jalili-Firoozinezhad, Mohammad Kazemi Ashtiani, Gilles Le Carrou, Shahragim Tajbakhsh, Hossein Baharvand
The availability of three-dimensional bioactive scaffolds with enhanced angiogenic capacity that have the capability to recruit tissue specific resident progenitors is of great importance for the regeneration of impaired skeletal muscle. Here we have investigated whether introduction of chemoattractant factors to tissue specific extracellular matrix (ECM) promotes cellular behavior in vitro as well as muscle progenitor recruitment and vascularization in vivo. We developed an interconnective macroporous sponge from decellularized skeletal muscle with maintained biochemical traits of the intact muscle...
May 16, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28509082/atg7-mediated-autophagy-is-involved-in-the-neural-crest-cell-generation-in-chick-embryo
#18
Guang Wang, En-Ni Chen, Chang Liang, Jianxin Liang, Lin-Rui Gao, Manli Chuai, Andrea Münsterberg, Yongping Bao, Liu Cao, Xuesong Yang
Autophagy plays a very important role in numerous physiological and pathological events. However, it still remains unclear whether Atg7-induced autophagy is involved in the regulation of neural crest cell production. In this study, we found the co-location of Atg7 and Pax7(+) neural crest cells in early chick embryo development. Upregulation of Atg7 with unilateral transfection of full-length Atg7 increased Pax7(+) and HNK-1(+) cephalic and trunk neural crest cell numbers compared to either Control-GFP transfection or opposite neural tubes, suggesting that Atg7 over-expression in neural tubes could enhance the production of neural crest cells...
May 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28506310/unexpected-evolutionarily-conserved-rapid-effects-of-viral-infection-on-oxytocin-receptor-and-tgf-%C3%AE-psmad3
#19
Yutong Liu, Irina Conboy
BACKGROUND: shRNA lentiviral vectors are extensively used for gene knockdowns in mammalian cells, and non-target shRNAs typically are considered the proper experimental control for general changes caused by RNAi. However, the effects of non-target lentivirus controls on the modulation of cell signaling pathways remain largely unknown. In this study, we evaluated the effect of control lentiviral transduction on oxytocin receptor (OXTR) expression through the ERK/MAPK pathway in mouse and human skeletal muscle cells, on myogenic activity, and in vivo on mouse muscle regeneration...
May 15, 2017: Skeletal Muscle
https://www.readbyqxmd.com/read/28498863/notch-ligands-regulate-the-muscle-stem-like-state-ex-vivo-but-are-not-sufficient-for-retaining-regenerative-capacity
#20
Hiroshi Sakai, Sumiaki Fukuda, Miki Nakamura, Akiyoshi Uezumi, Yu-Taro Noguchi, Takahiko Sato, Mitsuhiro Morita, Harumoto Yamada, Kunihiro Tsuchida, Shahragim Tajbakhsh, So-Ichiro Fukada
Myogenic stem cells are a promising avenue for the treatment of muscular disorders. Freshly isolated muscle stem cells have a remarkable engraftment ability in vivo, but their cell number is limited. Current conventional culture conditions do not allow muscle stem cells to expand in vitro with their bona fide engraftment efficiency, requiring the improvement of culture procedures for achieving successful cell-therapy for muscle disorders. Here we expanded mouse muscle stem cells and human myoblasts with Notch ligands, DLL1, DLL4, and JAG1 to activate Notch signaling in vitro and to investigate whether these cells could retain their engraftment efficiency...
2017: PloS One
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