GSE157467
GSE GEO Potentially relatedPersistent mRNA localization defects and cell death in ALS neurons caused by transient cellular stress
Relations
Summary
Neurodegeneration-associated mutations affect the dynamics of transient cytoplasmic stress granule (SG). However, it is unclear if and how aberrant SG behavior is linked to the downstream formation of protein aggregates and other molecular defects that persist after stress subsides. Using subcellular fractionation combined with RNA-seq (CeFra-seq) we characterize the global mRNA localization landscape in human pluripotent stem cell-derived motor neuron (PS-MN). Using CeFra-seq and quantitative proteomics, we find that transient stress leads to a widespread reshaping of mRNA and protein localization that recapitulates key molecular phenotypes of Amyotrophic Lateral Sclerosis (ALS). While the substantial reorganization of the global mRNA localization landscape is largely reversible in wild type PS-MNs, we find that cells harboring ALS-linked mutations in HNRNPA2B1 are unable to recover and display a delayed-onset increase in neuronal cell death in response to stress. Our findings reaffirm the importance of stress-induced molecular mechanisms in the formation of molecular disease pathology of ALS and highlight the importance of targeting SG-relevant molecular mechanisms in the development of therapeutic strategies.
Overall Design
Analysis of global mRNA localization in stem cells, stem cell-derived motor neurons and stem cell-derived motor neurons exposed to cellular stress and/or harboring ALS-associated mutations in HNRNPA2B1
Analysis (6 steps)
View Data Processing- Fastq files were trimmed for adapters using cutadapt
- Trimmed reads were aligned to the human genome build hg19 using STAR aligner
- seCLIP : Binding region peaks were identified based on read pileup densities (Clipper)
- seCLIP : Reproducible peaks were identified by comparing replicate read pileups along binding regions
- wiggle files
- peak text files
Supplementary Files (8)
GEO Samples (130)
Dataset Citations (1)
Potentially Related Publications (1)
This accession was text-mined from the PMC full text of these publications. It may be referenced for comparison or reused from another study rather than generated for them.
Data Files (10)
| Accession | File Name | Stored Type | Output Type | Mapping Assembly | Size | Download | |
|---|---|---|---|---|---|---|---|
| — | nuc_CR463_rec_rep1.fastq.gz | RNA-Seq | 645.6 MB | link | |||
| — | nuc_CR463_rec_rep2.fastq.gz | RNA-Seq | 1.1 GB | link | |||
| — | nuc_CR463_ut_rep1.fastq.gz | RNA-Seq | 1.9 GB | link | |||
| — | nuc_CR463_ut_rep2.fastq.gz | RNA-Seq | 1.2 GB | link | |||
| — | nuc_CR464_puro_rep1.fastq.gz | RNA-Seq | 2.3 GB | link | |||
| — | nuc_CR464_puro_rep2.fastq.gz | RNA-Seq | 1.1 GB | link | |||
| — | nuc_CR464_rec_rep1.fastq.gz | RNA-Seq | 1.2 GB | link | |||
| — | nuc_CR464_rec_rep2.fastq.gz | RNA-Seq | 1.3 GB | link | |||
| — | nuc_CR464_ut_rep1.fastq.gz | RNA-Seq | 1.1 GB | link | |||
| — | nuc_CR464_ut_rep2.fastq.gz | RNA-Seq | 1.4 GB | link |