Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA146049 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Cerebral palsy is primarily an upper motor neuron disease that results in a spectrum of progressive movement disorders. Secondary to the neurological lesion, muscles from patients with cerebral palsy are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in cerebral palsy is a response to aberrant neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response to cerebral palsy using microarrays and correlating the transcriptional data with functional measures. Hamstring biopsies from gracilis and semitendinosus muscles were obtained from a cohort of patients with cerebral palsy (n=10) and typically developing patients (n=10) undergoing surgery. Affymetrix HG-U133A 2.0 chips (n=40) were used and expression data was verified for 6 transcripts using quantitative real-time PCR, as well as for two genes not on the microarray. Chips were clustered based on their expression and those from patients with cerebral palsy clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n=1,398). Significantly altered genes were analyzed for over-representation among gene ontologies, transcription factors, pathways, microRNA and muscle specific networks. These results centered on an increase in extracellular matrix expression in cerebral palsy as well as a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and novel therapies. Skeletal muscle biopsies from both the gracilis and semitendinosus were obtained during surgery for 20 pediatric subjects for affymetrix microarray analysis. We obtained a group of 10 patients undergoing medial hamstring lengthening in the cerebral palsy group and 10 patients undergoing ACL reconstruction with hamstring autograft in the control group. This provided 40 microarrays in 4 groups to analyze the effect of cerebral palsy and also differences between muscles.
2012-11-21 | E-GEOD-31243 | biostudies-arrayexpress
Project description:Cerebral palsy is primarily an upper motor neuron disease that results in a spectrum of progressive movement disorders. Secondary to the neurological lesion, muscles from patients with cerebral palsy are often spastic and form debilitating contractures that limit range of motion and joint function. With no genetic component, the pathology of skeletal muscle in cerebral palsy is a response to aberrant neurological input in ways that are not fully understood. This study was designed to gain further understanding of the skeletal muscle response to cerebral palsy using microarrays and correlating the transcriptional data with functional measures. Hamstring biopsies from gracilis and semitendinosus muscles were obtained from a cohort of patients with cerebral palsy (n=10) and typically developing patients (n=10) undergoing surgery. Affymetrix HG-U133A 2.0 chips (n=40) were used and expression data was verified for 6 transcripts using quantitative real-time PCR, as well as for two genes not on the microarray. Chips were clustered based on their expression and those from patients with cerebral palsy clustered separately. Significant genes were determined conservatively based on the overlap of three summarization algorithms (n=1,398). Significantly altered genes were analyzed for over-representation among gene ontologies, transcription factors, pathways, microRNA and muscle specific networks. These results centered on an increase in extracellular matrix expression in cerebral palsy as well as a decrease in metabolism and ubiquitin ligase activity. The increase in extracellular matrix products was correlated with mechanical measures demonstrating the importance in disability. These data lay a framework for further studies and novel therapies.
2012-11-21 | GSE31243 | GEO
Project description:Cerebral palsy is caused be an upper motor neuron lesion which casues spasticity as well as secondary effects on muscle . Muscle from cerebral palsy patients is has been shown to be smaller, with more ECM and longer sarcomere lengths; We used microarrays to globally investigate the transcriptional adaptations of cerebral palsy muscle and research which muscle pathways are altered in the diseased state Experiment Overall Design: Muscle biopsies were taken from children undergoing surgery which exposed wrist muscle extensors (n=8) and flexors (n=8) in both cerebral palsy patients (n=6) and control patients (n=2) for RNA extraction and hybridization to Affymetrix GeneChips . Cerebral palsy patients were classified by a number of clinical scores.
2009-09-05 | E-GEOD-11686 | biostudies-arrayexpress
Project description:Limb contractures are a debilitating and progressive consequence of a wide range of pediatric conditions that affect skeletal muscles, including perinatal brain injury causing cerebral palsy (CP). While several rehabilitation therapies are currently used in the clinical setting, their long-term effectiveness in treating contractures is marginal since they do not change underlying muscle biological properties. Therefore, new therapies based on a biological understanding of contracture development are needed. Here we show that myoblast progenitor cells from contractured muscle in children with CP had higher rates of proliferation than control cells from typically developing children. This phenotype was associated with upregulation of DNMT3a and patterns of DNA hypermethylation and gene expression that favored cell expansion over quiescence. Treatment of CP progenitors with 5-azacytidine, a DNMT inhibitor and hypomethylating agent, normalized this epigenetic imprint and promoted exit from mitosis. Together with previous studies demonstrating reduction in myoblast differentiation capacity, these data suggest that mechanisms of early myofiber growth and establishment of an adult population of quiescent stem cells could be compromised in CP. Hypomethylating agents like 5-azacytidine could be used to rescue myogenesis and promote muscle growth in contractured muscle and thus may represent a new approach to treating this devastating condition
2021-08-04 | GSE181376 | GEO
Project description:Limb contractures are a debilitating and progressive consequence of a wide range of pediatric conditions that affect skeletal muscles, including perinatal brain injury causing cerebral palsy (CP). While several rehabilitation therapies are currently used in the clinical setting, their long-term effectiveness in treating contractures is marginal since they do not change underlying muscle biological properties. Therefore, new therapies based on a biological understanding of contracture development are needed. Here we show that myoblast progenitor cells from contractured muscle in children with CP had higher rates of proliferation than control cells from typically developing children. This phenotype was associated with upregulation of DNMT3a and patterns of DNA hypermethylation and gene expression that favored cell expansion over quiescence. Treatment of CP progenitors with 5-azacytidine (AZA), a DNMT inhibitor and hypomethylating agent, normalized this epigenetic imprint and promoted exit from mitosis. Together with previous studies demonstrating reduction in myoblast differentiation capacity, these data suggest that mechanisms of early myofiber growth and establishment of an adult population of quiescent stem cells could be compromised in CP. Hypomethylating agents like AZA could be used to rescue myogenesis and promote muscle growth in contractured muscle and thus may represent a new approach to treating this devastating condition
2021-04-02 | GSE171318 | GEO
Project description:Cerebral palsy is caused be an upper motor neuron lesion which casues spasticity as well as secondary effects on muscle . Muscle from cerebral palsy patients is has been shown to be smaller, with more ECM and longer sarcomere lengths We used microarrays to globally investigate the transcriptional adaptations of cerebral palsy muscle and research which muscle pathways are altered in the diseased state Keywords: Disease state analysis
2009-08-26 | GSE11686 | GEO
Project description:Unique Transcriptional Profile in Wrist Muscles From Cerebral Palsy Patients
| PRJNA106091 | ENA
Project description:Cerebral palsy (CP) represents a group of non-progressive clinically heterogeneous disorders that are characterized by motor impairment and early age-of-onset, frequently accompanied by co-morbidities. The cause of CP has historically been attributed to environmental stressors resulting in brain damage. While genetic risk factors are also implicated, guidelines for diagnostic assessment of CP do not recommend for routine genetic testing. Given numerous reports of etiologic copy number variations (CNVs) in other neurodevelopmental disorders, we used microarrays to genotype a population-based prospective cohort of children with CP and their parents. Here we identify de novo CNVs in 8/115 (7.0%) CP patients (~1% rate in controls). In four children, large chromosomal abnormalities deemed pathogenic were found, and they were significantly more likely to have severe neuro-motor impairments than those CP subjects without such alterations. Overall the CNV data would have impacted our diagnosis or classification of CP in 11/115 (9.6%) families. Dr. Maryam Oskoui* , Mr. Matthew Gazzellone* , Ms. Bhooma Thiruvahindrapuram , Dr. Mehdi Zarrei , Dr. John Andersen , Dr. John Wei , Dr. Zhouzhi Wang , Dr. Richard Wintle , Dr. Christian Marshall , Dr. Ronald Cohn , Dr. Rosanna Weksberg , Dr. James Stavropoulos , Dr. Darcy Fehlings , Dr. Michael Shevell, Dr. Stephen Scherer. Clinically Relevant Copy Number Variations Detected in Cerebral Palsy. Nature Communications, 2015. Following our rigorous quality control procedure, we successfully genotyped 147 proband samples from individuals with cerebral palsy (81 males and 66 females) and 282 samples obtained from parents (134 males and 148 females). This facilitated the identification of de novo and rare inherited copy number variations of clinical interest.
2015-07-28 | E-GEOD-70374 | biostudies-arrayexpress
Project description:A Dysregulated Proinflammatory Status in Preterm School-aged Children with PVL-induced Spastic Cerebral Palsy
| PRJNA118827 | ENA