GEO DataSets

(Submitter supplied) Efforts to genetically reverse C9orf72 pathology have been hampered by our incomplete understanding of the regulation of this complex locus. We generated five different genomic excisions at the C9orf72 locus in a patient-derived iPSC line and a WT line (11 total isogenic lines), and examined gene expression and pathological hallmarks of C9 FTD/ALS in motor neurons differentiated from these lines. Comparing the excisions in these isogenic series removed the confounding effects of different genomic backgrounds and allowed us to probe the effects of specific genomic changes. more...

Organism:

Homo sapiens

Type:

Methylation profiling by high throughput sequencing

Platform:

GPL28352

5 Samples

Download data: BAM, BED, BW

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

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL24676

56 Samples

Download data: NARROWPEAK, TXT

(Submitter supplied) N6-methyladenosine (m6A) is the most prevalent internal mRNA modification and regulates RNA metabolism. Repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). Here, we showed that m6A is downregulated in C9ORF72-ALS/FTD patient-derived iPSC-differentiated neurons and postmortem brain tissues. The global m6A hypomethylation leads to transcriptome-wide mRNA stabilization and upregulated gene expression, especially ones involved in synaptic activity and neuronal functions. more...

Organism:

Homo sapiens

Type:

Other

Platform:

GPL24676

28 Samples

Download data: NARROWPEAK

(Submitter supplied) N6-methyladenosine (m6A) is the most prevalent internal mRNA modification and regulates RNA metabolism. Repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). Here, we showed that m6A is downregulated in C9ORF72-ALS/FTD patient-derived iPSC-differentiated neurons and postmortem brain tissues. The global m6A hypomethylation leads to transcriptome-wide mRNA stabilization and upregulated gene expression, especially ones involved in synaptic activity and neuronal functions. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

18 Samples

Download data: TXT

(Submitter supplied) N6-methyladenosine (m6A) is the most prevalent internal mRNA modification and regulates RNA metabolism. Repeat expansion in C9ORF72 is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). Here, we showed that m6A is downregulated in C9ORF72-ALS/FTD patient-derived iPSC-differentiated neurons and postmortem brain tissues. The global m6A hypomethylation leads to transcriptome-wide mRNA stabilization and upregulated gene expression, especially ones involved in synaptic activity and neuronal functions. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Other

Platform:

GPL24676

10 Samples

Download data: TXT

(Submitter supplied) Nuclear RNA foci are often associated with mis-regulation of RNA processing in repeat expansion diseases. Here we report transcriptomic analysis of mice expressing expanded G4C2 repeats, the most common genetic cause of FTD/ALS. We show that the presence of numerous nuclear G4C2 repeat RNA foci does not cause extensive changes in RNA processing in this model organism.

Organism:

Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL13112

8 Samples

Download data: TXT

(Submitter supplied) Amyotrophic lateral sclerosis (ALS) is a severe neurodegenerative condition characterized by loss of motor neurons in the brain and spinal cord. Expansions of a hexanucleotide repeat (GGGGCC) in the noncoding region of the C9ORF72 gene are the most common cause of the familial form of ALS (C9-ALS), as well as frontotemporal lobar degeneration and other neurological diseases. How the repeat expansion causes disease remains unclear, with both loss of function (haploinsufficiency) and gain of function (either toxic RNA or protein products) proposed. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

8 Samples

Download data: TXT

(Submitter supplied) Hexanucleotide repeat expansions in the C9orf72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9FTD/ALS). The nucleotide repeat expansions are translated into dipeptide repeat (DPR) proteins, which are aggregation-prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene knockout screens for suppressors and enhancers of C9orf72 DPR toxicity in human cells. more...

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL21626 GPL21697

18 Samples

Download data: CSV

(Submitter supplied) To analyze the epigenomic landscape of neurodegeneration caused by ALS-associated protein aggregation, we developed a modified version of ATAC-seq that works on primary neurons. We discovered that C9orf72-ALS/FTD associated poly(PR) activated a remarkably specific signature of chromatin accessibility, involving transcriptional targets of the tumor suppressor gene p53. Our findings reveal an unexpected role of p53 as a mediator of neurodegeneration elicited by poly(PR) and provide an example of how ATAC-seq can now be applied to neurons to define mechanisms of neurodegeneration.

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing; Other

Platforms:

GPL21697 GPL21626 GPL21103

52 Samples

Download data: BW, CSV

(Submitter supplied) Sequencing of human iPS-derived motor neurons from fibroblasts of Amyotrophic lateral sclerosis patients with an M337V mutation in TARDBP and comparison with age matched healthy controls identify differences in glutamate receptor and mitochondrial calcium buffering channels.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

10 Samples

Download data: TSV

(Submitter supplied) The G4C2 hexanucleotide repeat expansion (HRE) in C9orf72 is the commonest cause of familial amyotrophic lateral sclerosis (ALS). A number of different methods have been used in an attempt to generate isogenic control lines using CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 and NHEJ by deleting the repeat region without replacing it with the normal repeat size, but typically this strategy carries the risk of creating indels and genomic instability. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL20301

12 Samples

Download data: TSV