Genomics

Dataset Information

0

Post-transcriptional remodelling is temporally deregulated during motor neurogenesis in human ALS models


ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE98289 | GEO | 2018/03/08

REPOSITORIES: GEO

Similar Datasets

2017-05-31 | GSE98288 | GEO
2017-06-10 | GSE99843 | GEO
2021-10-25 | GSE160133 | GEO
2021-09-09 | PXD022604 | Pride
2024-01-11 | GSE246397 | GEO
2023-07-21 | GSE214017 | GEO
2020-12-31 | GSE152983 | GEO
2023-01-01 | GSE144640 | GEO
2022-08-17 | GSE210969 | GEO
2020-06-01 | GSE142730 | GEO