Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ribo-depleted RNA-Seq Libraries From Huntington's Disease Brain

ABSTRACT: Transcriptional dysregulation is well documented in Huntington’s disease (HD) post-mortem brain. We previously identified gene expression profiles from both symptomatic and asymptomatic HD prefrontal cortex which characterize the effects of degeneration in disease versus normal brains. Transcriptional dysregulation in HD brain is well documented by these studies and others, but the extent and causes of this dysregulation remain unknown. Here, we present a large ribo-depleted RNA sequencing (rdRNA-Seq) dataset and novel bioinformatic methodology to further characterize transcriptional dysregulation in HD brain as it relates to disease variables, including CAG repeat size, age of symptom onset, and rate of neurodegeneration.

ORGANISM(S): Homo sapiens

PROVIDER: GSE159940 | GEO | 2020/10/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptome sequencing reveals aberrant alternative splicing in Huntington's disease

Project description:Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG expansion in the gene encoding Huntingtin (HTT). Transcriptome dysregulation is a major feature of HD pathogenesis, as revealed by a large body of work on gene expression profiling of tissues from human HD patients and mouse models. These studies were primarily focused on transcriptional changes affecting steady-state overall gene expression levels using microarray based approaches. A major missing component however has been the study of transcriptome changes at the post-transcriptional level, such as alternative splicing. Alternative splicing is a critical mechanism for expanding regulatory and functional diversity from a limited number of genes, and is particularly complex in the mammalian brain. Here we carried out a deep RNA-seq analysis of 7 human HD brains and 7 controls to systematically discover aberrant alternative splicing events and characterize potential associated splicing factors in HD. We identified 593 differential alternative splicing events between HD and control brains. Using an expanded panel of 54 brain tissues from patients and controls, we also identified 9 splicing factors exhibiting significantly altered expression levels in HD patient brains. Moreover, follow-up molecular analyses of one splicing factor PTBP1 revealed its impact on disease-associated splicing patterns in HD. Collectively, our data provide genomic evidence for widespread splicing dysregulation in HD brains, and suggest the role of aberrant alternative splicing in the pathogenesis of HD

2016-06-14 | GSE79666 | GEO

mRNA-Seq Expression profiling of human post-mortem BA9 brain tissue for Huntington's Disease and neurologically normal individuals

Project description:Huntington’s Disease (HD) is a devastating neurodegenerative disorder that is caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene. Transcriptional dysregulation in the human HD brain has been documented but is incompletely understood. Here we present a genome-wide analysis of mRNA expression in human prefrontal cortex from 20 HD and 49 neuropathologically normal controls using next generation high-throughput sequencing. Surprisingly, 19% (5,480) of the 28,087 confidently detected genes are differentially expressed (FDR<0.05) and are predominantly up-regulated. A novel hypothesis-free geneset enrichment method that dissects large gene lists into functionally and transcriptionally related groups discovers that the differentially expressed genes are enriched for immune response, neuroinflammation, and developmental genes. Markers for all major brain cell types are observed, suggesting that HD invokes a systemic response in the brain area studied. Unexpectedly, the most strongly differentially expressed genes are a homeotic gene set (represented by Hox and other homeobox genes), that are almost exclusively expressed in HD, a profile not widely implicated in HD pathogenesis. The significance of transcriptional changes of developmental processes in the HD brain is poorly understood and warrants further investigation. The role of inflammation and the significance of non-neuronal involvement in HD pathogenesis suggest anti-inflammatory therapeutics may offer important opportunities in treating HD.

2015-12-08 | GSE64810 | GEO

mRNA-Seq Expression profiling of human post-mortem BA9 brain tissue for Huntington's Disease and neurologically normal individuals

Project description:Huntingtonâs Disease (HD) is a devastating neurodegenerative disorder that is caused by an expanded CAG trinucleotide repeat in the Huntingtin (HTT) gene. Transcriptional dysregulation in the human HD brain has been documented but is incompletely understood. Here we present a genome-wide analysis of mRNA expression in human prefrontal cortex from 20 HD and 49 neuropathologically normal controls using next generation high-throughput sequencing. Surprisingly, 19% (5,480) of the 28,087 confidently detected genes are differentially expressed (FDR<0.05) and are predominantly up-regulated. A novel hypothesis-free geneset enrichment method that dissects large gene lists into functionally and transcriptionally related groups discovers that the differentially expressed genes are enriched for immune response, neuroinflammation, and developmental genes. Markers for all major brain cell types are observed, suggesting that HD invokes a systemic response in the brain area studied. Unexpectedly, the most strongly differentially expressed genes are a homeotic gene set (represented by Hox and other homeobox genes), that are almost exclusively expressed in HD, a profile not widely implicated in HD pathogenesis. The significance of transcriptional changes of developmental processes in the HD brain is poorly understood and warrants further investigation. The role of inflammation and the significance of non-neuronal involvement in HD pathogenesis suggest anti-inflammatory therapeutics may offer important opportunities in treating HD. 20 Huntington's Disease and 49 neurologically normal control samples from post-mortem human subjects

2015-12-08 | E-GEOD-64810 | biostudies-arrayexpress

Transcriptome sequencing reveals aberrant alternative splicing in Huntington's disease

Project description:Huntingtonâs disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG expansion in the gene encoding Huntingtin (HTT). Transcriptome dysregulation is a major feature of HD pathogenesis, as revealed by a large body of work on gene expression profiling of tissues from human HD patients and mouse models. These studies were primarily focused on transcriptional changes affecting steady-state overall gene expression levels using microarray based approaches. A major missing component however has been the study of transcriptome changes at the post-transcriptional level, such as alternative splicing. Alternative splicing is a critical mechanism for expanding regulatory and functional diversity from a limited number of genes, and is particularly complex in the mammalian brain. Here we carried out a deep RNA-seq analysis of 7 human HD brains and 7 controls to systematically discover aberrant alternative splicing events and characterize potential associated splicing factors in HD. We identified 593 differential alternative splicing events between HD and control brains. Using an expanded panel of 54 brain tissues from patients and controls, we also identified 9 splicing factors exhibiting significantly altered expression levels in HD patient brains. Moreover, follow-up molecular analyses of one splicing factor PTBP1 revealed its impact on disease-associated splicing patterns in HD. Collectively, our data provide genomic evidence for widespread splicing dysregulation in HD brains, and suggest the role of aberrant alternative splicing in the pathogenesis of HD RNA-seq analysis of the BA4 motor cortex of 7 control and 7 Huntington's disease patients. 1.5 ug of total RNA was used for RNA-seq library preparation using the TruSeqâ¢ Stranded mRNA LT Sample Prep Kit (Illumina). 100x2 bp paired-end RNA-seq reads were generated on a HiSeq 2000 sequencer.

2016-06-14 | E-GEOD-79666 | biostudies-arrayexpress

Molecular and cellular consequences of genetic knockout of Hdac2 and Hdac3 in striatal medium spiny neurons of Huntington's disease knock-in mice

Project description:Somatic expansion of the Huntington’s disease (HD) CAG repeat drives the rate of a pathogenic process resulting in neuronal cell death. Although mechanisms of neuronal toxicity are not well delineated, transcriptional dysregulation is a likely contributor. Chromatin modifiers are implicated in both mechanisms of CAG instability and transcriptional dysregulation. Here, we tested whether histone deacetylase genes Hdac2 and Hdac3 modify molecular and cellular phenotypes in HttQ111 knock-in mice using conditional knockouts in striatal medium-spiny striatal neurons (MSNs) exhibiting extensive CAG expansion and exquisite disease vulnerability. MSN-specific Hdac2 or Hdac3 knockout attenuated CAG expansion, with the Hdac2 knockout impacting nuclear huntingtin pathology. Hdac2 knockout resulted in a substantial transcriptional response that included reversal of transcriptional dysregulation elicited by the HttQ111 allele. Our results identify novel modifiers of CAG expansion in MSNs, providing testable mechanistic hypotheses, and a potentially complex relationship between Htt and Hdac2 with implications for targeting transcriptional dysregulation in HD.

2020-06-01 | GSE148440 | GEO

Transplanted Human Neural Stem Cells Rescue Phenotypes in zQ175 Huntington's Disease Mice and Innervate the Striatum

Project description:Long-term implantation of human NSCs in Huntington’s disease (HD) mice ameliorates behavioral deficits and reduces mutant Huntingtin accumulation. The human NSCs survive and differentiate into diverse neuronal populations, form connections, improve synaptic properties and show restoration of several transcriptional changes in HD mouse cells.

2023-11-06 | GSE245631 | GEO

Targeting H3K4 methylation as a therapeutic strategy for Huntington's disease (RNA-seq)

Project description:Transcriptional dysregulation is an early feature of Huntington's disease (HD). We observed gene-specific changes in H3K4me3 at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a novel chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin (Htt) expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective. Therefore, targeting this epigenetic signature may be an effective strategy to ameliorate the consequences of HD. mRNA-seq in wild type and R6/2 cortex and striatum at 8 and 12 weeks.

2013-07-18 | E-GEOD-48962 | biostudies-arrayexpress

The transcriptional modulator H2AFY marks Huntington's disease activity in men and mice

Project description:To accelerate the development of disease-modifying therapeutics for Huntington’s disease (HD), a dynamic biomarker of disease activity and treatment response is critically needed.

2011-09-01 | GSE24250 | GEO

Targeting H3K4 methylation as a therapeutic strategy for Huntington's disease (ChIP-seq)

Project description:Transcriptional dysregulation is an early feature of Huntington's disease (HD). We observed gene-specific changes in H3K4me3 at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a novel chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin (Htt) expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective. Therefore, targeting this epigenetic signature may be an effective strategy to ameliorate the consequences of HD. ChIP-seq for H3K4me3 in wild type and R6/2 cortex and striatum at 8 and 12 weeks.

2013-07-18 | E-GEOD-48960 | biostudies-arrayexpress

Targeting H3K4 methylation as a therapeutic strategy for Huntington's disease (RNA-seq)

2013-07-18 | GSE48962 | GEO