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Status |
Public on Mar 08, 2018 |
Title |
Post-transcriptional remodelling is temporally deregulated during motor neurogenesis in human ALS models |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Mutations causing amyotrophic lateral sclerosis (ALS) strongly implicate regulators of RNA-processing that are ubiquitously expressed throughout development. To understand the molecular impact of ALS-causing mutations on early neuronal development and disease, we performed transcriptomic analysis of differentiated human control and VCP-mutant induced pluripotent stem cells (iPSCs) during motor neurogenesis. We identify intron retention (IR) as the predominant splicing change affecting early stages of wild-type neural differentiation, targeting key genes involved in the splicing machinery. Importantly, IR occurs prematurely in VCP-mutant cultures compared with control counterparts; these events are also observed in independent RNAseq datasets from SOD1- and FUS-mutant motor neurons (MNs). Together with related effects on 3’UTR length variation, these findings implicate alternative RNA-processing in regulating distinct stages of lineage restriction from iPSCs to MNs, and reveal a temporal deregulation of such processing by ALS mutations. Thus, ALS-causing mutations perturb the same post-transcriptional mechanisms that underlie human motor neurogenesis.
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Overall design |
Bulk RNA-seq at different timepoints throughout a 35-day differentiation protocol that converted iPSC cells to highly enriched motor neurons.
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Contributor(s) |
Luisier R, Tyzack GE, Hall CE, Ule J, Luscombe NM, Patani R |
Citation(s) |
28564594, 29789581 |
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Submission date |
Apr 27, 2017 |
Last update date |
Jul 25, 2021 |
Contact name |
Raphaelle Luisier |
E-mail(s) |
raphaelle.luisier@gmail.com
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Phone |
0041762432198
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Organization name |
Idiap Research Institute
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Lab |
Genomics and Health Informatics
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Street address |
Rue Marconi 19, PO Box 592
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City |
Martigny |
State/province |
Valais |
ZIP/Postal code |
1920 |
Country |
Switzerland |
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Platforms (1) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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Samples (11)
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This SubSeries is part of SuperSeries: |
GSE98290 |
Post-transcriptional remodelling is temporally deregulated during motor neurogenesis in human ALS models |
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Relations |
BioProject |
PRJNA384598 |
SRA |
SRP105348 |