Molecular correlation between mouse retina and striatum in HD
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA894148 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22029306_1.fastq.gz | Fastqsanger.gz | |||
| SRR22029306_2.fastq.gz | Fastqsanger.gz | |||
| SRR22029307_1.fastq.gz | Fastqsanger.gz | |||
| SRR22029307_2.fastq.gz | Fastqsanger.gz | |||
| SRR22029308_1.fastq.gz | Fastqsanger.gz |
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Project description:Huntington’s disease (HD) is a devastating disorder caused by an aberrant expansion of CAG repeats in the HTT gene. Striatal dysfunction has been widely studied in HD mouse models as part of the basal ganglia, the main brain areas affected in patients that explain the most evident symptomatology. However, cumulative evidence indicates that the retina can also be functionally altered with consequences for visual function and circadian rhythms. Moreover, the retina is the most exposed part of the CNS that can be used for monitoring the health status of patients using non-invasive techniques and for treatment screenings in preclinical models. To establish the retina as an appropriate tissue for HD studies, it is first required to link retinal alterations at the cellular and molecular levels with those of the inner brain. In this work, we confirmed that the retinas of R6/1 mice were functionally and morphologically affected, and suffered a rearrangement of its transcriptome as extensive as in the striatum. Tissue-enriched genes were downregulated in both areas, but a neuroinflammation signature was specific to the R6/1 retina through the glial activation that was apparently absent in the striatum of the same animals. These phenomena were confirmed in the zQ175 strain, and were accompanied by a differential impairment of the autophagy system between both tissues that may have implications for autophagic-based therapies in HD. Overall, these results demonstrated the suitability of the retina as a research model for HD and general neurodegeneration.
2024-01-23 | GSE216520 | GEO
Project description:Temporal dynamics and mechanisms underlying epigenetic changes in Huntington’s disease (HD),a neurodegenerative disease primarily affecting the striatum, remain unclear. Using slow progressing HDknockinmice,we have generated chromatin immunoprecipitation coupled with sequencing data for RNA polymerase II and histone modifications associated with active enhancers (H3K27ac) and repressive chromatin (H3K27me3), from neuronal, non-neuronal and bulk striatal tissue at two early disease stages. Data integration with cell type-specific transcriptomic databases shows that the HD mutation early accelerates age-related reprogramming of neuronal and glial cell identities at both epigenetic and transcriptional levels. Circular chromosome conformation capture followed by sequencing data using HD mouse striatum showed alterations both at neuronal super-enhancer and CAG expanded disease loci. Using these data to model higher-order chromatin architecture indicated that HD CAG expansion mutation impairs chromatin insulation and gene regulation. Thus, both age-dependent and disease locus-specific mechanisms contribute to early remodelling of chromatin structure in HD striatum.
2020-10-16 | GSE144699 | GEO
Project description:Huntington's disease (HD) is a debilitating progressive neurodegenerative disorder that has profound effects on an individual's cognitive, motor, and behavioral functions. HD is caused by mutation in the huntingtin (HTT) gene that results in CAG repeat expansion and production of an aggregation-prone polyglutamine-containing protein (mHTT). The expression of mHTT causes selective degeneration, mainly in the striatum and cortex brain regions. Yet, the molecular signatures that underlie their selective sensitization remain incompletely characterized. In HD mouse models, we systematically employed immunopurification-mass spectrometry using HTT antibodies targeting non-overlapping epitopes to capture distinct sub-cellular pools of HTT complexes and postulate domain-specific interactions. We also identified mHTT- and tissue-dependent interactions at different disease stages, which were validated using targeted mass spectrometry and computational analysis of HD genetic modifiers. Among the polyQ-dependent, striatum-enriched interactions, we identified interaction with the mediator complex that results in its altered nuclear-cytoplasmic distribution. Integrating IP-MS data with thermal profiling of the mediator complex in HTT deficient cells supports an interaction interface with the mediator tail domain. Broadly, striatum-enriched HTT interactions highlight calcium homeostasis and ion transport at the synapse as sensitizing molecular signatures.
2024-04-10 | MSV000094509 | MassIVE
Project description:Gene expression profiling of striatum in R6/2 Huntington’s disease (HD) model mouse. Striatum gene set contained gene expression alterations in other neuronal populations, such as oligodendrocyte, astrocyte, microglia and interneuron.
2020-06-03 | GSE113929 | GEO
Project description:We intend to screen altered genes after overexpression of miR-196a in HD transgenic mice. Two transgenic mouse lines were used in this study, including HD transgenic mice and HD transgenic mice overexpressing miR-196a. The mice were all at approximate 12 months of age. At this point, HD transgenic mice showed severve motor dysfunctions, whereas HD transgenic mice overexpressing miR-196a displayed mild motor dysfunctions. We used the striatum tissues from 2 HD transgenic mice and 3 HD transgenic mice overexpressing miR-196a. The mice were all at approximate 12 months of age. Two technique repeats were performed for each sample.
2013-05-30 | E-GEOD-47500 | biostudies-arrayexpress
Project description:To gain insight into how mutant Huntingtin (mHTT) CAG repeat length may modify Huntington’s disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat length. We find repeat length dependent transcriptional signatures are prominent in the striatum, less so in cortex, and minimal in the liver. Co-expression network analyses reveal 13 striatal and 5 cortical modules that are highly correlated with CAG length and age, and that are preserved in HD models and some in the patients. Top striatal modules implicate mHTT CAG length and age in graded impairment of striatal medium spiny neuron identity gene expression and in dysregulation of cAMP signaling, cell death, and protocadherin genes. Importantly, we used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at both RNA and protein levels and validated 21 striatal module genes as modifiers of mHtt toxicities in vivo.
2016-02-16 | PXD003442 | Pride
Project description:This laboratory focuses on the molecular mechanisms of neuropsychiatric and neurodegenerative disorders Our goal is to elucidate mechanisms by which regulated expression of proteoglycans and glycosylation-related genes contribute to neurodegenerative diseases involving the striatum. A number of studies have demonstrated that neural proteoglycans are involved structural organization of the striatum and formation of dopaminergic connections to and from the striatum. Several proteoglycans are also associated with neuronal regeneration and some have been shown to be components of filamentous inclusions found in neurodegenerative disorders. In addition, the localization and proper function of dopamine receptors, which are predominantly expressed in the striatum, are governed by N-linked glycosylation events. Huntingtonís Disease (HD), a progressive neurodegenerative disorder, results in selective degeneration of the striatum. This is caused by a mutation in the protein, huntingtin, however, the mechanisms responsible for neuronal degeneration remain unknown. Similar to the brains of HD patients, HD transgenic mice exhibit huntingtin protein aggregation and nuclear inclusions, selective degeneration of dopamine neurons in the striatum and dopamine receptor dysfunction. In this study, the gene expression patterns of HD transgenic mice were analyzed. Four groups, pre-symptomatic HD mice (6 weeks old), WT control (6 weeks), post symptomatic HD (16 weeks), and WT control (16 weeks), were hybridized and analyzed using the GLYCOv2 array. Each group was hybridized in triplicate.
2011-03-02 | E-GEOD-27588 | biostudies-arrayexpress
Project description:Huntington’s disease (HD) involves marked early neurodegeneration in the striatum whereas the cerebellum is relatively spared despite the ubiquitous expression of full-length mutant huntingtin, implying that inherent tissue-specific differences determine susceptibility to the HD CAG mutation. To understand this tissue specificity, we compared early mutant huntingtin-induced gene expression changes in striatum to those in cerebellum in young Hdh CAG knock-in mice, prior to onset of evident pathological alterations. Endogenous levels of full-length mutant huntingtin caused qualitatively similar, but quantitatively different gene expression changes in the two brain regions. Importantly, the quantitatively different responses in striatum and cerebellum in mutant mice were well accounted for by the intrinsic molecular differences in gene expression between striatum and cerebellum in wild-type animals. Tissue-specific gene expression changes in response to the HD mutation, therefore, appear to reflect the different inherent capacities of these tissues to buffer qualitatively similar effects of mutant huntingtin. These findings highlight a role for intrinsic quantitative tissue differences in contributing to HD pathogenesis, and likely to other neurodegenerative disorders exhibiting tissue-specificity, thereby guiding the search for effective therapeutic interventions. Total RNA was isolated from striatum and cerebellum of Hdh CAG knock-in mice (HdhQ111/HdhQ111) and wild-type mice (Hdh+/Hdh+, 3~10 weeks) for gene expression profiling using Affymetrix MG430 2.0 arrays.
2011-08-22 | E-GEOD-9038 | biostudies-arrayexpress
Project description:Wild-type CBAxC57BL/6 (6 weeks of age) and HD Exon 1 R6/2 CBAxC57BL/6 (6 weeks of age). Control groups for two drug studies. All animals injected with normal saline 30-60 minutes prior to sacrifice. Keywords: parallel sample
2011-10-12 | E-GEOD-1980 | biostudies-arrayexpress
Project description:To try to investigate the mechanism behind the adaptive phenotypes observed in a mice model model of HD crossed with mGluR5 knockout, we analyzed whether mutated huntingtin (Htt) expression in a mGluR5 null background could be altering the expression of genes that might be involved in the pattern of Htt aggregation and HD-related locomotor alterations. In this data set, we include analysis of gene expression in striatum of mice with four different genotypes: HdhQ20/Q20/mGluR5+/+; HdhQ20/Q20/mGluR5-/- ; HdhQ111/Q111/mGluR5+/+ ; HdhQ111/Q111/mGluR5-/-
2013-08-28 | GSE50379 | GEO