Expression data of iPSC-derived motor neurons from healthy donor, FALS, SALS, and drug-treated them
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE106382 | GEO | 2018/06/30
REPOSITORIES: GEO
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2014-10-15 | E-GEOD-52917 | biostudies-arrayexpress
Project description:Knowledge about the nature and timepoint of pathomolecular alterations preceding onset of symptoms in amyotrophic lateral sclerosis (ALS) is largely lacking. It could not only pave the way for valuable therapeutic targets but might also govern future concepts of pre-manifest disease modifying treatments. MicroRNAs (miRNAs) are central regulators of transcriptome plasticity and participate in pathogenic cascades and/or mirror cellular adaptation to insults. We obtained expression profiles of miRNAs as well as other non-coding RNAs (ncRNAs) in the serum of sporadic ALS patients (sALS), familial ALS cases (fALS), asymptomatic mutation carriers and healthy controls. We observed a strikingly homogenous ncRNA profile in fALS patients that, to a large extend, was independent to the underlying disease gene and different to heterogeneous ncRNA signatures in sALS patients. Moreover, we identified 68 significantly dysregulated ncRNAs in pre-manifest ALS mutation carriers, more than 20 years before the estimated time window of disease onset. 91% of ncRNA alterations in mutation carriers overlapped with the fALS patients revealing progressive changes towards and during the disease. Our data thus demonstrate a high epigenetic heterogeneity amongst sALS patients and suggest common denominators regarding molecular pathogenesis of different ALS genes. We describe the earliest pathomolecular alterations in ALS known to date, which provide a basis for the development of predictors of disease onset as well as the discovery of novel therapeutic targets and strongly argue for studies evaluating pre-symptomatic disease-modifying treatment in ALS.
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2012-07-25 | E-GEOD-39644 | biostudies-arrayexpress
Project description:To assess RNA regulation in FALS for gene expression and alternative processing of RNA in the motor neuron precurssors (MPCs) Amyotrophic lateral sclerosis (ALS) is a late-onset motor neuron disorder. Although its neuropathology is well understood, the cellular and molecular mechanisms that lead to the initiation and progression of this disease are yet to be elucidated due to limitations in the currently available human genetic data. In this study, we generated induced pluripotent stem cells (iPSC) from two familial ALS (FALS) patients with a missense mutation in the fused-in sarcoma (FUS) gene carrying the heterozygous FUS H517D mutation, and the isogenic iPSCs with the homozygous FUS H517D mutation obtained by genome editing from the healthy control iPSCs. These cell-derived motor neurons mimicked several neurodegenerative phenotypes. A part of the mutant FUS protein was localized outside the nucleus and co-localized with stress granules under stress conditions. Moreover, FALS motor neurons showed more apoptotic activity than did control motor neurons. Exon array analysis using motor neuron precursor cells (MPCs) combined with CLIP-seq data sets revealed aberrant gene expression and/or splicing pattern in FALS-MPCs. These results suggest that iPSC-derived motor neurons are a useful tool for analyzing the pathogenesis of human motor neuron disorders.
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Project description:Expression data of iPSC-derived motor neurons from healthy donor, FALS, SALS, and drug-treated them
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