Chromatin accessibilities in C9HRE ALS/FTD patient cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA925486 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:ATAC-seq was utilized to profile the chromatin status in ALS/FTD patient cells carrying the hexanuleotide repeat expansion in C9orf72.
2023-02-10 | GSE223255 | GEO
Project description:ATAC-Seq analysis of the chromatin accessibilities in C9HRE ALS/FTD patient cells
| PRJNA925663 | ENA
Project description:Using ChIP-seq to profile the genomic binding of DAXX in control and C9HRE ALS/FTD patient B lymphocytes.
2023-02-10 | GSE223401 | GEO
Project description:Dysregulation of RNA processing contributes to neurodegenerative diseases, especially amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Expansion of an intronic (GGGGCC)n repeat within the C9ORF72 gene is the most common cause of both FTD and ALS (C9-FTD/ALS), characterized with aberrant repeat RNA foci in the nucleus and noncanonical translation-produced dipeptide repeat (DPR) protein inclusions in the cytoplasm. Here we elucidate that the (GGGGCC)n repeat RNA co-localizes with nuclear speckles and alters their phase separation properties and granule dynamics. Moreover, the essential nuclear speckle scaffold protein SRRM2 is sequestered into the poly-GR cytoplasmic inclusions in C9-FTD/ALS mouse model and patient postmortem tissues, exacerbating the nuclear speckle dysfunction. Impaired nuclear speckle integrity induces global exon-skipping and intron retention in human iPSC-derived neurons. Similar alternative splicing changes can be found in patient postmortem tissues. This work identified novel molecular mechanism of global RNA splicing defects by impaired nuclear speckle function in C9-FTD/ALS and revealed novel potential biomarkers or therapeutic targets.
2024-08-23 | GSE248404 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-02-10 | GSE223259 | GEO
Project description:Single cell RNA sequencing data was collected from 150 day old human cortical organoid slice cultures grown at the air-liquid interface (ALI-COs) from control and ALS/FTD patient-specific induced pluripotent stem cell (iPSC) lines harbouring the C9ORF72 hexanucleotide repeat expansion mutation. Data collection included ALI-COs derived from the following iPSC lines: WTSli042-B (WTS42b) and A18945 (EpiC) for healthy controls, CS30iALS-C9nxx (CS30) and CS29iALS-C9nxx (CS29) for ALS/FTD, and CS29iALS-C9n1.ISOxx (ISO29), a mutation-corrected isogenic line. A total of 148,223 cells were processed over two batches.
2021-10-21 | GSE180122 | GEO
Project description: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. The m6A modification in the C9ORF72 intron sequence preceding the expanded repeats enhances RNA degradation via the nuclear reader YTHDC1. The m6A reduction leads to increased accumulation of repeat RNA and poly-dipeptides. Moreover, the antisense RNA can also be regulated by m6A. Elevating m6A level significantly reduces both sense and antisense repeat RNA and poly-dipeptides, rescues global mRNA homeostasis, and improves survival of C9ORF72-ALS/FTD patient neurons.
2023-06-09 | GSE203580 | GEO
Project description: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. The m6A modification in the C9ORF72 intron sequence preceding the expanded repeats enhances RNA degradation via the nuclear reader YTHDC1. The m6A reduction leads to increased accumulation of repeat RNA and poly-dipeptides. Moreover, the antisense RNA can also be regulated by m6A. Elevating m6A level significantly reduces both sense and antisense repeat RNA and poly-dipeptides, rescues global mRNA homeostasis, and improves survival of C9ORF72-ALS/FTD patient neurons.
2023-06-09 | GSE203579 | GEO
Project description: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. The m6A modification in the C9ORF72 intron sequence preceding the expanded repeats enhances RNA degradation via the nuclear reader YTHDC1. The m6A reduction leads to increased accumulation of repeat RNA and poly-dipeptides. Moreover, the antisense RNA can also be regulated by m6A. Elevating m6A level significantly reduces both sense and antisense repeat RNA and poly-dipeptides, rescues global mRNA homeostasis, and improves survival of C9ORF72-ALS/FTD patient neurons.
2023-06-09 | GSE203578 | GEO
Project description:Recently, we identified missense mutations in CCNF that are causative of familial and sporadic amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). CCNF encodes for cyclin F, a substrate recognition component of an E3-ubiquitin ligase. Mutations in CCNF directly implicates disruption in the ubiquitin-proteasome system in the pathogenesis of ALS/FTD. In this study we used an unbiased proteomic screening workflow using the proximity-based ligation method, BioID, to identify putative interaction partners of cyclin F. In doing so, we found over 100 putative interaction partners of cyclin F. Notably, we demonstrated that cyclin F closely associates with a number of essential paraspeckle proteins, which are stress-responsive proteins that have recently been implicated in ALS pathogenesis. We further demonstrate that SCFcyclin F mediates the direct ubiquitylation and subsequent proteasomal degradation of RBM14, a core component of the paraspeckle complex. This degradation is defective when cyclin F carries an ALS/FTD-causing mutation, leading to RBM14 accumulation in primary neurons upon proteasome inhibition. Additionally, analysis of ALS patient post-mortem tissue revealed that RBM14 levels were significantly reduced in post-mortem ALS patient motor cortex and significantly reduced in the neurons of spinal cord tissue. Together, our data indicate that defects in RBM14 homeostasis, which can be due to defects in cyclin F-mediated degradation, may be a common factor underlying ALS/FTD disease pathogenesis.
2021-03-18 | PXD014163 | Pride