H3K4me3 ChIP-Seq profiles of control and huntington's disease iPSC-derived medium spiny neuron-like cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE144493 | GEO | 2020/03/01
REPOSITORIES: GEO
Similar Datasets
Project description:HD and control patient-derived induced pluripotent stem cells were used to generate medium spiny neuron-like cells. Three control in triplicate, one control in duplicate, one HD samples with CAG repeat length in typical adult onset range in triplicate and one in duplicate, and five HD samples with CAG repeat length in typical juvenile onset range in triplicate were differentiated as biological growth replicate (separate differentiations) into medium spiny neuron-like cells. Total RNA was isolated using the Qiagen RNeasy Kit and QIAshredders for cell lysis. 1 µg of RNA with RIN values >9 were used for library preparation using the strand specific Illumina TruSeq Total RNA protocol. Libraries were sequenced on the HiSeq 2500 using 100 cycles to obtain paired-end 100 reads at >50M reads per sample.
2020-03-01 | GSE144518 | GEO
Project description:HD and control patient-derived induced pluripotent stem cells were used to generate medium spiny neuron (MSN)-like cells. Three control in triplicate, one control in duplicate, one HD samples with CAG repeat length in typical adult onset range in triplicate and one in duplicate, and five HD samples with CAG repeat length in typical juvenile onset range in triplicate were differentiated as biological growth replicate (separate differentiations) into medium spiny neuron-like cells. Total RNA was isolated using the Qiagen RNeasy Kit and QIAshredders for cell lysis. 1 µg of RNA with RIN values >9 were used for library preparation using the strand specific Illumina TruSeq Total RNA protocol. Libraries were sequenced on the HiSeq 2500 using 100 cycles to obtain paired-end 100 reads at >50M reads per sample.
2020-03-01 | GSE144559 | GEO
Project description:HD and control patient-derived induced pluripotent stem cells were used to generate medium spiny neuron-like cells. One control and one HD sample with CAG repeat length in typical adult onset range were differentiated into medium spiny neuron-like cells. Cells were dissociated into single cell suspension and single cell viability for each sample was determined (86.9% for control, 80.9% for HD). Cells were processed using 10x genomics single cell platform. Libraries were sequenced on the HiSeq 4000 using 100 cycles to obtain paired-end 100 reads at >50M reads per cell. The estimated number of cells sampled was 5,070 (control) and 3,829 (HD) with an average number of reads per cell at 31,675 (control) and 41,939 (HDQ). After QC filtering, the data were aggregated using Cell Ranger and gene-by-cell expression matrices generated and used as input for Seurat and Scanpy.
2020-03-01 | GSE144477 | GEO
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:HD and control patient-derived induced pluripotent stem cells were used to generate medium spiny neuron-like cells. four control in duplicate and three HD samples in duplicate with CAG repeat length in juvenile onset range were differentiated as biological growth replicates (separate differentiations) into medium spiny neuron-like cells. Cells were treated with LNPs with siRNA for knockdown of PIAS1 or a luciferase control. Total RNA was isolated using the Qiagen RNeasy Kit and QIAshredders for cell lysis. For mouse data WT and HET GFP+ micro-dissected flash frozen brain regions (striatum) were homogenized in TRIzol reagent (Invitrogen) and RNA were collected and purified using RNEasy Mini kit (Qiagen). Mice were treated with AAV2/1 expressing either a miRNA against Pias1 (miPias1.3), a control scrambled miRNA (miSafe). 1 µg of RNA with RIN values >8 were used for library preparation using the strand specific Illumina TruSeq mRNA protocol. Libraries were sequenced on the HiSeq 4000 using 100 cycles to obtain paired-end 100 reads.
2021-01-01 | GSE162349 | GEO
Project description:HuntingtonÂs disease (HD) is a devastating neurodegenerative disease, with out effective treatment. Despite significant advances, our understanding of how an expanded CAG repeat in the amino terminus of the large ubiquitously expressed HD gene product remains incomplete. Augmented adult neurogenesis in response to acute and chronic injury, including HuntingtonÂs disease, has been demonstrated, but its role development, disease, and recovery is largely unknown, as are the factors controlling it. The HD gene product, huntingtin (htt) is know to interact with a number of transcription factors which subsequently influence gene expression. Understanding the factors involved in controlling neurogenesis in response to disease would bridge a significant knowledge gap and have tremendous therapeutic potential. We propose to identify transcripts responsible for CAG repeat facilitated neurogenesis. Our hypothesis is that expanded CAG repeats in the HuntingtonÂs disease gene facilitates neurogenesis by altering transcription of genes critical in neurogenesis. We have developed a model in which mouse embryonic stem cells (ESC) with expanded CAG repeats have facilitated neurogenesis. In this model more ESC with expanded CAG repeats transition to neuronal precursors and then develop into mature neurons more rapidly than control ESC. We propose to compare the gene expression profiles between ESC with expanded CAG repeats and control ESCs on days 4 and 6 of neuronal differentiation. Initial studies indicate that key transcriptional differences are occurring at these time points. Control ECS and a an ESC line with150 CAG repeats will be differentiated in triplicate, and RNA isolated form each replicate. It is anticipated that comparison of gene expression between the control and CAG repeat lines at each time point will identify transcripts involved in CAG repeat facilitated neurogenesis. Observed differences at day 4 may be more relevant to the transition from ESC to neuronal precursor whereas differences at day 6 may be more relevant to the neuronal precursor to neuron transition.
2008-06-16 | E-GEOD-9760 | biostudies-arrayexpress
Project description:Huntington’s disease (HD) is an incurable hereditary neurodegenerative disorder, which manifests itself as a loss of GABAergic medium spiny (GABA MS) neurons in the striatum and caused by an expansion of the CAG repeat in exon 1 of the huntingtin gene. There is no cure for HD, existing pharmaceutical can only relieve its symptoms. Here, induced pluripotent stem cells were established from patients with low CAG repeat expansion in the huntingtin gene, and were then efficiently differentiated into GABA MS-like neurons under defined culture conditions. Analysis of differentially expressed genes between Huntington’s disease and wild type iPSCs derived GABA MS-like neurons has been performed.
2016-02-04 | GSE77558 | GEO
Project description:Progressive motor alterations and selective death of striatal medium spiny neurons (MSNs) are key pathological hallmarks of Huntington's disease (HD), a neurodegenerative condition caused by a CAG trinucleotide repeat expansion in the coding region of the huntingtin (HTT) gene. Most research has focused on the pathogenic effects of the resultant protein product(s); however, growing evidence indicates that expanded CAG repeats within mutant HTT mRNA and derived small CAG repeat RNAs (sCAG) participate in HD pathophysiology. The individual contribution of protein versus RNA toxicity to HD pathophysiology remains largely uncharacterized and the role of other classes of small RNAs (sRNA) that are strongly perturbed in HD is uncertain. Here, have injected vehicle, CTL-sRNA (obtained from non-affected individuals) or HD-sRNA (obtained from patients with HD) from different brain areas (putamen, PT; cortex, CTX and cerebellum, CB) into the striatum of wild type (WT) mice and demonstrate that sRNA produced in the putamen and cortex of HD patients are sufficient to induce HD pathology in vivo. We have performed small RNA (sRNA) sequencing of the human samples used for injection. Here we describe the procedure to obtain and sequence human sRNA isolated from the different brain areas.
2021-02-16 | GSE165663 | GEO
Project description:Huntington’s disease (HD), caused by a CAG repeat expansion in the huntingtin (HTT) gene, is characterized by abnormal protein aggregates and motor and cognitive dysfunction. Htt protein is ubiquitously expressed, but the striatal medium spiny neuron (MSN) is most susceptible to neuronal dysfunction and death. Abnormal gene expression represents a core pathogenic feature of HD, but the relative roles of cell-autonomous and non-cell-autonomous effects on transcription remain unclear. To determine the extent of cell-autonomous dysregulation in the striatum in vivo, we examined genome-wide RNA expression in symptomatic D9-N171-98Q (a.k.a. DE5) transgenic mice in which the forebrain expression of the first 171 amino acids of human Htt with a 98Q repeat expansion is limited to MSNs. Microarray data generated from these mice were compared to those generated on the identical array platform from a pan-neuronal HD mouse model, R6/2, carrying two different CAG repeat lengths, and a relatively high degree of overlap of changes in gene expression was revealed. We further focused on known canonical pathways associated with excitotoxicity, oxidative stress, mitochondrial dysfunction, dopamine signaling and trophic support, among others. While genes related to excitotoxicity, dopamine signaling and trophic support, were altered in both DE5 and R6/2 transgenic mice, which may be either cell-autonomous or non-cell-autonomous,, genes related to mitochondrial dysfunction, oxidative stress and the peroxisome proliferator-activated receptor are primarily affected in DE5 transgenic mice, indicating cell autonomous mechanisms Overall, our results demonstrate that HD-induced dysregulation of the striatal transcriptome can be largely attributed to intrinsic effects of mutant Htt,,such that mutant Htt-induced effects in cortical neurons is not necessary for striatal dysfunction/degeneration. Striatum from DE5 transgenic mice vs. wt littermate controls
2011-01-01 | E-GEOD-25232 | biostudies-arrayexpress
Project description:Huntingtons disease (HD) is a devastating neurodegenerative disease, with out effective treatment. Despite significant advances, our understanding of how an expanded CAG repeat in the amino terminus of the large ubiquitously expressed HD gene product remains incomplete. Augmented adult neurogenesis in response to acute and chronic injury, including Huntingtons disease, has been demonstrated, but its role development, disease, and recovery is largely unknown, as are the factors controlling it. The HD gene product, huntingtin (htt) is know to interact with a number of transcription factors which subsequently influence gene expression. Understanding the factors involved in controlling neurogenesis in response to disease would bridge a significant knowledge gap and have tremendous therapeutic potential. We propose to identify transcripts responsible for CAG repeat facilitated neurogenesis. Our hypothesis is that expanded CAG repeats in the Huntingtons disease gene facilitates neurogenesis by altering transcription of genes critical in neurogenesis. We have developed a model in which mouse embryonic stem cells (ESC) with expanded CAG repeats have facilitated neurogenesis. In this model more ESC with expanded CAG repeats transition to neuronal precursors and then develop into mature neurons more rapidly than control ESC. We propose to compare the gene expression profiles between ESC with expanded CAG repeats and control ESCs on days 4 and 6 of neuronal differentiation. Initial studies indicate that key transcriptional differences are occurring at these time points. Control ECS and a an ESC line with150 CAG repeats will be differentiated in triplicate, and RNA isolated form each replicate. It is anticipated that comparison of gene expression between the control and CAG repeat lines at each time point will identify transcripts involved in CAG repeat facilitated neurogenesis. Observed differences at day 4 may be more relevant to the transition from ESC to neuronal precursor whereas differences at day 6 may be more relevant to the neuronal precursor to neuron transition. Keywords: time-course
2007-12-04 | GSE9760 | GEO