Similar Datasets
Project description:Most human cancers originate from high-turnover tissues, while low-proliferating tissues, like skeletal muscle, exhibit a lower incidence of tumor development. In Duchenne muscular dystrophy (DMD), which induces increased skeletal muscle regeneration, tumor incidence is increased. Rhabdomyosarcomas (RMSs), a rare and aggressive type of soft tissue sarcoma, can develop in this context, but the impact of DMD severity on RMS development and its cell of origin are poorly understood. Here, we show that RMS latency is affected by DMD severity and that muscle stem cells (MuSCs) can give rise to RMS in dystrophic mice. We report that even before tumor formation, MuSCs exhibit increased self-renewal and an expression signature associated with RMSs. These cells can form tumorspheres in vitro and give rise to RMSs in vivo. Finally, we show that the inflammatory genes Ccl11 and Rgs5 are involved in RMS growth. Together, our results show that DMD severity drives MuSC-mediated RMS development.
| S-EPMC6853774 | biostudies-literature
Project description:Muscle stem cells give rise to rhabdomyosarcomas in severe model of Duchenne muscular dystrophy
| PRJNA508732 | ENA
Project description:Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle disorder resulting in muscle weakness and cardiomyopathy. MicroRNAs have shown to play a significant role in muscle development, metabolism, and disease pathologies. We demonstrated that miR-486 expression is reduced in DMD muscles and its expression levels correlate with dystrophic disease severity. miR-486 knockout mice developed disrupted myofiber architecture, decreased myofiber size, decreased locomotor activity, increased fibrosis, and metabolic defects that were exacerbated on the dystrophic mdx5cv background. We integrated RNA-sequencing and chimeric eCLIP-sequencing data to identify direct in vivo targets of miR-486 and associated dysregulated gene signatures in skeletal muscle. Together, our studies identify miR-486 as a driver of muscle remodeling in DMD, a useful biomarker for dystrophic disease progression, and highlight chimeric eCLIP-sequencing as a useful tool to identify direct in vivo microRNA target transcripts.
2022-05-04 | GSE173821 | GEO
Project description:Duchenne muscular dystrophy (DMD) is an X-linked progressive muscle disorder resulting in muscle weakness and cardiomyopathy. MicroRNAs have shown to play a significant role in muscle development, metabolism, and disease pathologies. We demonstrated that miR-486 expression is reduced in DMD muscles and its expression levels correlate with dystrophic disease severity. miR-486 knockout mice developed disrupted myofiber architecture, decreased myofiber size, decreased locomotor activity, increased fibrosis, and metabolic defects that were exacerbated on the dystrophic mdx5cv background. We integrated RNA-sequencing and chimeric eCLIP-sequencing data to identify direct in vivo targets of miR-486 and associated dysregulated gene signatures in skeletal muscle. Together, our studies identify miR-486 as a driver of muscle remodeling in DMD, a useful biomarker for dystrophic disease progression, and highlight chimeric eCLIP-sequencing as a useful tool to identify direct in vivo microRNA target transcripts.
2022-10-01 | GSE178772 | GEO
Project description:gene expression data is from RNA extracted from muscle biopsy samples taken from boys with Duchenne muscular dystrophy (DMD) or pathologically normal controls (CTRL). Each muscle biospy was examined in detail histologically by Dr. Eric P. Hoffman at Children's National Medical Center to determine stage of disease. In addition, the absence or presence of dystrophin was determined via western blot analyses. We utilized Human U133 2.0 arrays to examine the transcriptome of each muscle, and then we compared differential gene expression between DMD patient muscles and CTRL muscules. We set the FDR p value for significance at 0.05 and at least a 1.5 fold difference in DMD/CTRL compared differential gene exrpression between DMD versus Control
2016-07-01 | E-GEOD-38417 | biostudies-arrayexpress
Project description:Duchenne muscular dystrophy is a severe, progressive, muscle-wasting disease that leads to difficulties with movement and, eventually, to the need for assisted ventilation and premature death. The disease is caused by mutations in DMD (encoding dystrophin) that abolish the production of dystrophin in muscle. Muscles without dystrophin are more sensitive to damage, resulting in progressive loss of muscle tissue and function, in addition to cardiomyopathy. Recent studies have greatly deepened our understanding of the primary and secondary pathogenetic mechanisms. Guidelines for the multidisciplinary care for Duchenne muscular dystrophy that address obtaining a genetic diagnosis and managing the various aspects of the disease have been established. In addition, a number of therapies that aim to restore the missing dystrophin protein or address secondary pathology have received regulatory approval and many others are in clinical development.
| S-EPMC10557455 | biostudies-literature
Project description:In order to understand the chronic hypoxia (CH) effect upon the absence of dystrophin, Drosophila melanogaster wild type and the model for DMD (dmDys), in which all dystrophins expression was knocked out by iRNA, were exposed to high altitude hypoxia (hypobaric hypoxia) during a 16-day climbing period reaching the summit of Mount McKinley (6194 meters above sea level). Furthermore, dmDys and Drosophila wild type were exposed to normobaric hypoxia (hypoxic chamber) following the same oxygen levels observed during the climbing expedition and to normoxic conditions for comparison. Affymetrix GeneChip® profiling was performed for individual flies from each experimental group. CH-dmDys differentially expressed 1281 genes, whereas control group differentially expressed 57 genes. Eight heat shock protein genes detected in the CH-dmDys microarray study were down-regulated, instead of up-regulated as seen in wild type hypoxic flies. This result suggests a differential gene expression response to CH, which could affect muscle performance.These results suggest that dmDys is more sensitive to CH due to reduced muscle function and hypoxic stress response. In order to understand the chronic hypoxia (CH) effect upon the absence of dystrophin, Drosophila melanogaster wild type and the model for DMD (dmDys), in which all dystrophins expression was knocked out by iRNA, were exposed to high altitude hypoxia (hypobaric hypoxia) during a 16-day climbing period reaching the summit of Mount McKinley (6194 meters above sea level). Furthermore, dmDys and Drosophila wild type were exposed to normobaric hypoxia (hypoxic chamber) following the same oxygen levels observed during the climbing expedition and to normoxic conditions for comparison. Affymetrix GeneChip® profiling was performed for individual flies from each experimental group. CH-dmDys differentially expressed 1281 genes, whereas control group differentially expressed 57 genes. Eight heat shock protein genes detected in the CH-dmDys microarray study were down-regulated, instead of up-regulated as seen in wild type hypoxic flies. This result suggests a differential gene expression response to CH, which could affect muscle performance.These results suggest that dmDys is more sensitive to CH due to reduced muscle function and hypoxic stress response. Overall design: Adults wild type and dystrophic flies (3-5 days old) were exposed to hypobaric hypoxia for two weeks during the summer expedition to Mount McKinley, Alaska (6194 MASL). Another set of wild types and dystrophic flies were exposed to normobaric hypoxia according to the table I obtained during the climbing expedition. During the expedition, the flies were maintained in vials with regular molasses and covered by thermo isolation to avoid low temperature, keeping the temperature at 25C. The experiment performed in the laboratory also used vials with regular molasses and at 25C. Table I. Expedition log book for mount McKinley ascent. Information obtained during the ascent and summit of Mount McKinley, June 1st to June 16th of 2007. The oxygen pressure (PO2) was calculated from the barometric pressure. GNB means go and back from the mentioned point. DAY In order to understand the chronic hypoxia (CH) effect upon the absence of dystrophin, Drosophila melanogaster wild type and the model for DMD (dmDys), in which all dystrophins expression was knocked out by iRNA, were exposed to high altitude hypoxia (hypobaric hypoxia) during a 16-day climbing period reaching the summit of Mount McKinley (6194 meters above sea level). Furthermore, dmDys and Drosophila wild type were exposed to normobaric hypoxia (hypoxic chamber) following the same oxygen levels observed during the climbing expedition and to normoxic conditions for comparison. Affymetrix GeneChip® profiling was performed for individual flies from each experimental group. CH-dmDys differentially expressed 1281 genes, whereas control group differentially expressed 57 genes. Eight heat shock protein genes detected in the CH-dmDys microarray study were down-regulated, instead of up-regulated as seen in wild type hypoxic flies. This result suggests a differential gene expression response to CH, which could affect muscle performance.These results suggest that dmDys is more sensitive to CH due to reduced muscle function and hypoxic stress response. In order to understand the chronic hypoxia (CH) effect upon the absence of dystrophin, Drosophila melanogaster wild type and the model for DMD (dmDys), in which all dystrophins expression was knocked out by iRNA, were exposed to high altitude hypoxia (hypobaric hypoxia) during a 16-day climbing period reaching the summit of Mount McKinley (6194 meters above sea level). Furthermore, dmDys and Drosophila wild type were exposed to normobaric hypoxia (hypoxic chamber) following the same oxygen levels observed during the climbing expedition and to normoxic conditions for comparison. Affymetrix GeneChip® profiling was performed for individual flies from each experimental group. CH-dmDys differentially expressed 1281 genes, whereas control group differentially expressed 57 genes. Eight heat shock protein genes detected in the CH-dmDys microarray study were down-regulated, instead of up-regulated as seen in wild type hypoxic flies. This result suggests a differential gene expression response to CH, which could affect muscle performance.These results suggest that dmDys is more sensitive to CH due to reduced muscle function and hypoxic stress response. Overall design: Adults wild type and dystrophic flies (3-5 days old) were exposed to hypobaric hypoxia for two weeks during the summer expedition to Mount McKinley, Alaska (6194 MASL). Another set of wild types and dystrophic flies were exposed to normobaric hypoxia according to the table I obtained during the climbing expedition. During the expedition, the flies were maintained in vials with regular molasses and covered by thermo isolation to avoid low temperature, keeping the temperature at 25C. The experiment performed in the laboratory also used vials with regular molasses and at 25C. Table I. Expedition log book for mount McKinley ascent. Information obtained during the ascent and summit of Mount McKinley, June 1st to June 16th of 2007. The oxygen pressure (PO2) was calculated from the barometric pressure. GNB means go and back from the mentioned point. DAY LOCATION ALTITUDE m PO2 mmHg (%) 1 Base Camp 2200 123.6 (16.3%) 2 Base Camp 2200 123.6 (16.3%) 3 Base Camp 2200 123.6 (16.3%) 4 Ski Hill 2400 120.7 (15.9%) 5 Kahiltna Pass 2950 113.0 (14.9%) 6 Motorcycle Hill 3350 107.7 (14.2%) 7 Motorcycle Hill 3350 107.7 (14.2%) 8 GNB from Motorcycle 4150 (5 hours) 97.7 (12.9%) 9 Medical Camp 4350 95.3 (12.5%) 10 GNB from Medical Camp 4150 (5 hours) 97.7 (12.9%) 11 Medical Camp 4350 95.3 (12.5%) 12 GNB from Medical Camp 4900 89.0 (11.7%) 13 Medical Camp 4350 95.3 (12.5%) 14 High Camp 5250 85.1 (11.2%) 15 Summit 6194 (0.3 hours) 75.4 (9.9%) 16 High Camp 5250 85.1 (11.2%)
2010-07-31 | E-GEOD-15879 | biostudies-arrayexpress
Project description:Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle degeneration. No treatments are currently available to prevent the disease. While the muscle enriched microRNA, miR-133b, has been implicated in muscle biogenesis, its role in DMD remains unknown. To assess miR-133b function in DMD-affected skeletal muscles, we genetically ablated miR-133b in the mdx mouse model of DMD. In the absence of miR-133b, the tibialis anterior muscle of juvenile and adult mdx mice is populated by small muscle fibers and exhibits increased fibrosis, characterized by thickened interstitial space. Additional analysis revealed that loss of miR-133b exacerbates DMD-pathogenesis partly by altering satellite cell numbers and through widespread transcriptomic changes. These include known miR-133b targets as well as genes involved in cell proliferation and fibrosis. Altogether, our data demonstrate that skeletal muscles utilize miR-133b to mitigate the deleterious effects of DMD.
2020-08-15 | GSE156267 | GEO
Project description:gene expression data is from RNA extracted from muscle biopsy samples taken from boys with Duchenne muscular dystrophy (DMD) or pathologically normal controls (CTRL). Each muscle biospy was examined in detail histologically by Dr. Eric P. Hoffman at Children's National Medical Center to determine stage of disease. In addition, the absence or presence of dystrophin was determined via western blot analyses. We utilized Human U133 2.0 arrays to examine the transcriptome of each muscle, and then we compared differential gene expression between DMD patient muscles and CTRL muscules. We set the FDR p value for significance at 0.05 and at least a 1.5 fold difference in DMD/CTRL
2016-07-01 | GSE38417 | GEO
Project description:Large-animal models for Duchenne muscular dystrophy (DMD) are crucial for the evaluation of diagnostic procedures and treatment strategies. Pigs cloned from male cells lacking DMD exon 52 (DMDΔ52) exhibit molecular, clinical and pathological hallmarks of DMD, but die before sexual maturity and cannot be propagated by breeding. Therefore, we generated female DMD+/- carriers. A single founder animal had 11 litters with 29 DMDY/-, 34 DMD+/- as well as 36 male and 29 female wild-type offspring. Breeding with F1 and F2 DMD+/- carriers resulted in an additional 114 DMDY/- piglets. With intensive neonatal management, the majority survived for 3-4 months, providing statistically relevant cohorts for experimental studies. Pathological investigations and proteome studies of skeletal muscles and myocardium confirmed the resemblance to human disease mechanisms. Importantly, DMDY/- pigs displayed progressive myocardial fibrosis and increased expression of connexin-43, associated with significantly reduced left ventricular ejection fraction, at 3 months. Furthermore, behavioral tests provided evidence for impaired cognitive ability. Our breeding cohort of DMDΔ52 pigs and standardized tissue repositories provide important resources for studying DMD disease mechanisms and for testing novel treatment strategies.
| S-EPMC8688409 | biostudies-literature