GEO DataSets

(Submitter supplied) Down syndrome (DS) is the most common genetic cause of cognitive disability. However, it is largely unclear how the triplication of a small gene subset may impinge on diverse aspects of DS brain physio-pathology. Here, we took a multi-omics approach and simultaneously analyze by RNA-seq and proteomics the expression signature of two diverse regions of human postmortem DS brains. We found that the overexpression of triplicated genes triggered global expression dysregulations differentially affecting transcripts, miRNA and proteins involved in both known and novel candidate pathways. more...

Organism:

Homo sapiens

Type:

Non-coding RNA profiling by high throughput sequencing

Platform:

GPL24676

42 Samples

Download data: TXT

(Submitter supplied) Down syndrome (DS) is the most common genetic cause of cognitive disability. However, it is largely unclear how triplication of a small gene subset may impinge on diverse aspects of DS brain physiopathology. Here, we took a multi-omic approach and simultaneously analyzed by RNA-seq and proteomics the expression signatures of two diverse regions of human postmortem DS brains. We found that the overexpression of triplicated genes triggered global expression dysregulation, differentially affecting transcripts, miRNAs, and proteins involved in both known and novel biological candidate pathways. more...

Organism:

Homo sapiens

Type:

Non-coding RNA profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platform:

GPL24676

84 Samples

Download data

(Submitter supplied) Down syndrome (DS) is the most common genetic cause of cognitive disability. However, it is largely unclear how the triplication of a small gene subset may impinge on diverse aspects of DS brain physio-pathology. Here, we took a multi-omics approach and simultaneously analyze by RNA-seq and proteomics the expression signature of two diverse regions of human postmortem DS brains. We found that the overexpression of triplicated genes triggered global expression dysregulations differentially affecting transcripts, miRNA and proteins involved in both known and novel candidate pathways. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

42 Samples

Download data: TXT

(Submitter supplied) Down syndrome (DS), a genetic condition leading to intellectual disability, is characterized by triplication of human chromosome 21. Neuropathological hallmarks of DS include abnormal central nervous system development that manifests during gestation and extends throughout life. As a result, newborns and adults with DS exhibit cognitive and motor deficits and fail to meet typical developmental and lack independent life skills. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL13730

128 Samples

Download data: CEL, XLS

(Submitter supplied) Down syndrome (DS) is the most frequent cause of human congenital mental retardation. Cognitive deficits in DS result from perturbations of normal cellular processes both during development and in adult tissues, but the mechanisms underlying DS etiology remain poorly understood. To assess the ability of iPSCs to model DS phenotypes, as a prototypical complex human disease, we generated bona-fide DS and wild-type (WT) non-viral iPSCs by episomal reprogramming. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

54 Samples

Download data: TXT

(Submitter supplied) A major challenge in Down syndrome (DS) is to understand how the extra-dose of functional chromosome 21 (HSA21) genetic elements can impact on the tissue-specific transcriptome to contribute to phenotypic alterations. MiRNAs are post-transcriptional modulators with genome-wide regulatory effects. Five microRNAs have been identified in HSA21 that are present in triple copy in DS individuals. Interestingly, in the Ts65Dn mouse model of DS two of these miRNAs, miR-155 and miR-802, are also triplicated resulting in its overexpression. more...

Organism:

Mus musculus

Type:

Expression profiling by array

Platform:

GPL13912

16 Samples

Download data: TXT

(Submitter supplied) Basal forebrain cholinergic neuron (BFCN) degeneration is a hallmark of Down syndrome (DS) and Alzheimer's disease (AD). Current therapeutics in these disorders have been unsuccessful in slowing disease progression, likely due to poorly understood complex pathological interactions and dysregulated pathways. The Ts65Dn trisomic mouse model recapitulates both cognitive and morphological deficits of DS and AD, including BFCN degeneration and has shown lifelong behavioral changes due to maternal choline supplementation (MCS). more...

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL21103

24 Samples

Download data: RESULTS, TXT

(Submitter supplied) In this study we performed a systematic analysis of the non-coding RNA (ncRNA) transcriptomes of the Down Syndrome (DS) developing hippocampus using the DS mouse model Dp16(1)Yey. DS, caused by the trisomy of chromosome 21 (HSA21) is the most frequent human chromosomal disorder. Hippocampal-dependent learning and memory impairment is one of the most significant deficits of DS. ncRNAs: microRNA (miRNA), long non-coding RNA (lncRNA), and circular RNA (circRNA) have been increasingly revealed to be participating in various biological activities, especially in the brain development and neuronal functions. more...

Organism:

Mus musculus

Type:

Non-coding RNA profiling by high throughput sequencing; Expression profiling by high throughput sequencing

Platforms:

GPL21493 GPL17021

6 Samples

Download data: TXT

(Submitter supplied) Down syndrome (DS), caused by triplication of human chromosome 21 (HSA21), is the most common genetic origin of intellectual disability. Despite the limited success of current pharmacological interventions, little has been achieved to reverse the abnormal brain developmental in DS. Here, using human induced pluripotent stem cell (hiPSC)-based brain organoid and in vivo human neuronal chimeric mouse brain models, we demonstrate that the HSA21 genes OLIG1 and OLIG2 exhibit distinct temporal expression patterns during neuronal differentiation. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18573

6 Samples

Download data: XLSX

(Submitter supplied) Trisomy 21 (Ts21) or Down syndrome (DS) is the most common genetic cause of intellectual disability. To investigate the consequences of Ts21 on human brain development, we have systematically analyzed the transcriptome of dorsolateral prefrontal cortex (DFC) and cerebellar cortex (CBC) using exon array mapping in DS and matched euploid control brains spanning from prenatal development to adulthood. We identify hundreds of differentially expressed (DEX) genes in the DS brains, many of which exhibit temporal changes in expression over the lifespan. To gain insight into how these DEX genes may cause specific DS phenotypes, we identified functional modules of co-expressed genes using several different bioinformatics approaches, including WGCNA and gene ontology analysis. A module comprised of genes associated with myelination, including those dynamically expressed over the course of oligodendrocyte development, was amongst those with the great levels of differential gene expression. Using Ts65Dn mouse line, the most common rodent model of DS, w e observed significant and novel defects in oligodendrocyte maturation and myelin ultrastructure; establishing a correlative proof-of-principle implicating myelin dysgenesis in DS. Thus, examination of the spatio-temporal transcriptome predicts specific cellular and functional events in the DS brain and is an outstanding resource for determining putative mechanisms involved in the neuropathology of DS.

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL5175

116 Samples

Download data: CEL

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens; Mus musculus

Type:

Methylation profiling by array; Methylation profiling by high throughput sequencing

Platforms:

GPL13534 GPL13112

134 Samples

Download data: BEDGRAPH, BW

(Submitter supplied) Background: Trisomy 21 causes Down syndrome (DS), but the mechanisms by which the extra chromosome leads to deficient intellectual and immune function are not well understood. Results: Here, we profile CpG methylation in DS and control cerebral and cerebellar cortex of adults and cerebrum of fetuses. We purify neuronal and non-neuronal nuclei and T-lymphocytes and find biologically relevant genes with DS-specific methylation (DS-DM) in brain cells. more...

Organism:

Mus musculus

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL13112

3 Samples

Download data: BEDGRAPH, BW

(Submitter supplied) Background: Trisomy 21 causes Down syndrome (DS), but the mechanisms by which the extra chromosome leads to deficient intellectual and immune function are not well understood. Results: Here, we profile CpG methylation in DS and control cerebral and cerebellar cortex of adults and cerebrum of fetuses. We purify neuronal and non-neuronal nuclei and T-lymphocytes and find biologically relevant genes with DS-specific methylation (DS-DM) in brain cells. more...

Organism:

Homo sapiens

Type:

Methylation profiling by array

Platform:

GPL13534

131 Samples

Download data: TXT

(Submitter supplied) Trisomy of chromosome 21, the genetic cause of Down syndrome, has the potential to alter expression of genes on chromosome 21, as well as other locations throughout the genome. These transcriptome changes are likely to underlie the Down syndrome clinical phenotypes. We have employed RNA-seq to undertake an in-depth analysis of transcriptome changes resulting from trisomy of chromosome 21, using induced pluripotent stem cells (iPSCs) derived from a single individual with Down syndrome. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

12 Samples

Download data: TXT

(Submitter supplied) The goal of this study was to define molecular overlap between Down syndrome and Fragile X syndrome using human pluripotent stem cells (hPSCs) and in vitro derived glutamatergic neurons.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL16791

40 Samples

Download data: CSV