94d4bd98-f576-439f-92f7-773793ad108a - samples
Ontology highlight
ABSTRACT:
PROVIDER: EGAD00001009105 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:MTM-HD - fibroblast RNAseq. 57 samples from controls, pre-HD and early-HD patients.
| EGAD00001009104 | EGA
Project description:MTM-HD - skeletal muscle RNAseq. 57 samples from controls, pre-HD and early-HD patients.
| EGAD00001009106 | EGA
Project description:We examined whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in Huntington disease (HD) patients. Under the MTM-HD study we generated large, high-quality human datasets from skeletal muscle, skin and adipose tissue, as well as primary human fibroblast lines to probe molecular changes in human pre-manifest and early manifest HD patients. We document the involvement of inflammation, energy metabolism and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials.
| EGAS00001006473 | EGA
Project description:We examined whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in Huntington disease (HD) patients. Under the MTM-HD study we generated large, high-quality human datasets from skeletal muscle, skin and adipose tissue, as well as primary human fibroblast lines to probe molecular changes in human pre-manifest and early manifest HD patients. We document the involvement of inflammation, energy metabolism and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials.
| EGAS00001006474 | EGA
Project description:We examined whether peripheral tissues can serve as a source of readily accessible biological signatures at the RNA and protein level in Huntington disease (HD) patients. Under the MTM-HD study we generated large, high-quality human datasets from skeletal muscle, skin and adipose tissue, as well as primary human fibroblast lines to probe molecular changes in human pre-manifest and early manifest HD patients. We document the involvement of inflammation, energy metabolism and extracellular vesicle homeostasis. This demonstrates the potential to identify biological signatures from peripheral tissues in HD suitable as biomarkers in clinical trials.
| EGAS00001006472 | EGA
Project description:Direct neuronal conversion of fibroblasts from Huntington’s disease (HD) patients to striatal medium spiny neurons (MSNs) has been shown to recapitulate neurodegenerative pathology of HD. Here, we carried out comparative analyses between reprogrammed MSNs from patients at different disease stages to investigate age-associated molecular processes driving neurodegeneration. We found that neuronal death was manifested in reprogrammed MSNs from symptomatic HD patients (HD-MSNs) compared to MSNs derived from younger, pre-symptomatic patients (pre-HD-MSNs) and healthy controls. Dissecting the differential cellular state between HD-MSNs and pre-HD-MSNs by transcriptome and chromatin accessibility analyses identified miR-29b-3p, whose age-associated upregulation impairs autophagic function via human-specific targeting of STAT3. Reducing miR-29b-3p or treating with G2-115, a glibenclamide analog, increased the resilience of HD-MSNs against neurodegeneration by promoting autophagy, demonstrating that the autophagic decline during aging in HD underlies MSN degeneration and pointing to potential approaches for enhancing autophagy and resilience of MSNs against degeneration in HD.
2022-09-15 | GSE194242 | GEO
Project description:Direct neuronal conversion of fibroblasts from Huntington’s disease (HD) patients to striatal medium spiny neurons (MSNs) has been shown to recapitulate neurodegenerative pathology of HD. Here, we carried out comparative analyses between reprogrammed MSNs from patients at different disease stages to investigate age-associated molecular processes driving neurodegeneration. We found that neuronal death was manifested in reprogrammed MSNs from symptomatic HD patients (HD-MSNs) compared to MSNs derived from younger, pre-symptomatic patients (pre-HD-MSNs) and healthy controls. Dissecting the differential cellular state between HD-MSNs and pre-HD-MSNs by transcriptome and chromatin accessibility analyses identified miR-29b-3p, whose age-associated upregulation impairs autophagic function via human-specific targeting of STAT3. Reducing miR-29b-3p or treating with G2-115, a glibenclamide analog, increased the resilience of HD-MSNs against neurodegeneration by promoting autophagy, demonstrating that the autophagic decline during aging in HD underlies MSN degeneration and pointing to potential approaches for enhancing autophagy and resilience of MSNs against degeneration in HD.
2022-09-15 | GSE194241 | GEO
Project description:Post mortem human brain tissue comparison between HD patients and controls from 3 brain regions - cerebellum, frontal cortex [BA4, BA9] and caudate nucleus. Gene expression analysed using linear models from LIMMA package in Bioconductor suite. Experiment Overall Design: Large sample sizes were used to examine brain tissue gene expression at various stages of HD pathology. Three brain regions were profiled, compared and analysed for differential gene expression. The broad aim was to capture early stage gene expression changes in HD brains.
2009-09-12 | E-GEOD-3790 | biostudies-arrayexpress
Project description:We investigated gene expression signatures in subcutaneous adipose tissue obtained from control subjects, premanifest HD gene carriers and manifest HD subjects with the aim to identify gene expression changes and signalling pathway alterations in adipose tissue relevant to HD. Gene expression was assessed using Affymetrix GeneChip® Human Gene 1.0 ST Array. Target genes were technically validated using real-time quantitative PCR and the expression signature was validated in an independent subject cohort.
2016-03-20 | GSE73655 | GEO
Project description:The constant increase in the obese and overweight population creates opportunities for novel therapeutic innovations to allow people to eat without getting fat and getting sick. Here, fed a hyperlipidic diet (HD)C57BL6 thimet oligopeptidase null (THOP1-/-) male mice were shown to gain only 25% (females gained 60%) of the weight gained by control wild type (WT) mice. Distinct from WT mice,THOP1-/- fed HD exhibited normal blood glucose levels and no insulin resistance. THOP1-/-fed HD phenotype benefits also include regular blood cholesterol levels, reduced fat in adipose and liver tissues, increased adipose tissue adrenergic-stimulated lipolysis, and greater resistance and endurance on treadmill running tests at high intensity. THOP1-/-compared to WT have alterations on the expression levels of specific genes and microRNAs related to obesity. Intracellular peptides that had their relative levels altered in THOP1-/-were shown to modulate the expression levels of genes and mature microRNAs associated to obesity, in 3T3L1 adipocyte. The ubiquitous existence of intracellular peptides in different cells of different species suggests a broader biological significance of the present results, connecting proteasomal protein degradation to protein synthesis. These exciting results suggest THOP1 and intracellular peptides as novel therapeutic targets to control obesity and obesity-associated diseases.
2020-02-24 | PXD016265 | Pride