Homo sapiens
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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:Development of muscle contractures are common in Cerebral palsy (CP) and characterized by high muscle stiffness that limits function and mobility. The state of the cell types within muscle, particularly muscle stem cells (MuSCs) and fibro-adipogenic progenitors (FAPs), are largely unknown. The aim of this study was to leverage single cell RNA sequencing technology to determine how specific cell types are altered in contracture. CP MuSCs demonstrated significant upregulation of fibrotic genes (ACTA2) and down regulation of myogenic genes (MYF5) compared to typically developing MuSCs. The most dramatically up-regulated genes in FAPs in CP were also major fibrotic components (COL1A1). Interacting signals between FAPs, MuSCs, and immune cells, such as TNF signaling between macrophages and FAPs, were identified that support contracture progression. The study reveals specific genes and signals as therapeutic targets to reduce muscle contracture in children with CP.
2026-06-18 | GSE309114 | 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:Stem Cells in Muscle Contractures of Children with Cerebral Palsy have Decreased Myogenic and Increased Fibrotic Transcripts
| PRJNA1333979 | ENA
Project description:Unique Transcriptional Profile in Wrist Muscles From Cerebral Palsy Patients
| PRJNA106091 | ENA
Project description:Cerebral Palsy (CP) is a group of neurodevelopmental disorders characterized by persistent motor and posture impairments. Its molecular mechanisms remain poorly understood, and there is a lack of reliable blood-based biomarkers. This study employed circRNA-seq technology to analyze the expression profiles of circRNAs in peripheral blood from 3 children with cerebral palsy and 3 healthy controls.
2026-06-08 | GSE334222 | GEO