Project description:Amyotrophic lateral sclerosis and primary lateral sclerosis are two syndromic variants within the motor neurone disease spectrum. Whilst primary lateral sclerosis is associated with loss of upper motor neurons and a more benign disease course up to 17yrs, amyotrophic lateral sclerosis is caused by loss of both upper and lower motor neurons and has an average disease course of 2-3 years. The majority of cases are sporadic, thereby limiting the availability of cellular models for investigating pathogenic disease mechanisms. The aim of the present study was to evaluate fibroblasts as a cellular model for sporadic amyotrophic lateral sclerosis and primary lateral sclerosis, to establish whether disease-related dysregulated biological processes recapitulate those seen in the central nervous system and to elucidate pathways that distinguish between the two disease phenotypes. We used microarray analysis to determine the differences in gene expression between fibroblasts derived from skin biopsies taken from sporadic amyotrophic lateral sclerosis and primary lateral sclerosis neurologically normal human controls
Project description:Amyotrophic lateral sclerosis (ALS) is a rapidly progressive and fatal disease. Although astrocytes are increasingly recognized contributors to the underlying pathogenesis, the uniformity of their reactive transformation in different genetic forms of ALS remains unresolved. Here we begin to systematically examine this issue by performing RNA sequencing on highly enriched and serum-free human induced pluripotent stem cell derived astrocytes from patients with VCP, SOD1 and FUS mutations. The RNA-seq samples in this collection have been used to reveal that diverse fALS mutations lead to molecularly distinct reactive transformation in their basal state.
Project description:Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease mainly affecting upper and lower motoneurons (MNs). In the last decades, several genes have been associated to the familial form of this disorder (fALS), thus depicting an extremely complex pathogenic landscape. The aim of this study was to identify convergent molecular underpinnings shared by ALS cases characterized by mutations in different genes using human induced pluripotent stem cells (hiPSCs).
Project description:This study was designed to identify gene expression changes in skeletal muscle that could define reliably the degree of the severity of Amyotrophic lateral sclerosis (ALS). All samples were from human biopsies, either from healthy muscles or from muscle whose patients were clearly diagnosed as having Amyotrophic Lateral Sclerosis (ALS)
Project description:Sequencing of human iPS-derived motor neurons from fibroblasts of Amyotrophic lateral sclerosis patients with an M337V mutation in TARDBP and comparison with age matched healthy controls identify differences in glutamate receptor and mitochondrial calcium buffering channels.
Project description:Astrocyte responses to neuronal injury may be beneficial or detrimental to neuronal recovery, but the mechanism that determines these different responses are poorly understood. Transcriptional analysis showed that EphB1 induces a protective inflammatory signature in astrocytes, which is distinct from the response evoked by interleukin (IL)-6, which is known to have both pro- and anti-inflammatory properties. We demonstrate that this beneficial EphB1 induced signaling pathway is disrupted in astrocytes derived from human induced pluripotent stem cells (iPSC) of amyotrophic lateral sclerosis (ALS) patients.
Project description:Astrocyte responses to neuronal injury may be beneficial or detrimental to neuronal recovery, but the mechanism that determines these different responses are poorly understood. Transcriptional analysis showed that EphB1 induces a protective inflammatory signature in astrocytes, which is distinct from the response evoked by interleukin (IL)-6, which is known to have both pro- and anti-inflammatory properties. We demonstrate that this beneficial EphB1 induced signaling pathway is disrupted in astrocytes derived from human induced pluripotent stem cells (iPSC) of amyotrophic lateral sclerosis (ALS) patients.
Project description:The purpose of this experiment was to compare the differences in transcript levels between RNA samples collected from fibroblasts from healthy control patients, amyotrophic lateral sclerosis (ALS) patients carrying an expanded GGGGCC repeat mutation in the chromosome 9 open reading frame 72 gene and ALS patients with a mutation in the SOD1 gene.
Project description:In this study, we used human motor neurons derived from induced pluripotent stem cell lines (N1) to identify universal transcriptomic signatures of MCI-186 cellular effects, to highlight novel pathways responsible for its biological activity, and to unravel potential molecular actions in amyotrophic lateral sclerosis. Total RNA was extrated from cells after 24h exposure to 10μM MCI-186 or vehicle and subjected to RNA sequencing.
