An emergent disease-associated motor neuron state precedes cell death in a mouse model of ALS [multiome]
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ABSTRACT:
PROVIDER: PRJNA1311612 | ENA |
REPOSITORIES: ENA
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Project description:To uncover molecular determinants of motor neuron degeneration and selective vulnerability in amyotrophic lateral sclerosis (ALS), we performed longitudinal single-nucleus RNA sequencing, paired single-nucleus RNA and ATAC sequencing, and MERFISH spatial transcriptomics from control and SOD1-G93A mouse spinal cords. For the final snRNA-seq analysis, control experiments from Blum et al., Nat Neurosci, 2021 (GEO accession: GSE161621) were also used.
2025-08-27 | GSE306675 | GEO
Project description:An emergent disease-associated motor neuron state precedes cell death in a mouse model of ALS [scRNA-Seq]
| PRJNA1311614 | ENA
Project description:To uncover molecular determinants of motor neuron degeneration and selective vulnerability in amyotrophic lateral sclerosis (ALS), we performed longitudinal single-nucleus RNA sequencing, paired single-nucleus RNA and ATAC sequencing, and MERFISH spatial transcriptomics from control and SOD1-G93A mouse spinal cords. For the final snRNA-seq analysis, control experiments from Blum et al., Nat Neurosci, 2021 (GEO accession: GSE161621) were also used.
2025-08-27 | GSE306676 | GEO
Project description:Differentiated motor neurons from hiPSC derived from peripheral nerve fibroblasts of sporadic ALS patients and evaluated the gene expression profile by means microarray-linked to specific analysis tools. Two-condition experiment, ALS patients motor neurons vs. controls. Biological replicates: 3 ALS replicates, 3 control replicates.
2015-04-25 | E-GEOD-68240 | biostudies-arrayexpress
Project description:Gene expression profiling has been performed on motor cortex and spinal cord homogenates and of sporadic ALS cases and controls, to identify genes and pathways differentially expressed in ALS. More recent studies have combined the use of laser capture microdissection (LCM) with gene expression profiling to isolate the motor neurons from the surrounding cells, such as microglia and astrocytes, in order to determine those genes differentially expressed in the vulnerable cell population â i.e. motor neuron. The aim of this study was to determine the gene expression profiles from a small subset of cases which all carry mutations in the CHMP2B gene. These mutations have been found to be associated with the lower motor neuron dominant variant of ALS. Expression profiles from isolated motor neurons in CHMP2B-related ALS cases were compared to those from control motor neurons, in order to establish the pathways implicated in CHMP2B-related motor neuronal cell death.
2010-03-07 | E-GEOD-19332 | biostudies-arrayexpress
Project description:Recent genetic studies of ALS patients have identified several forms of ALS that are associated with mutations in RNA binding proteins. In animals or cultured cells, such defects broadly affect RNA metabolism. This raises the question of whether all forms of ALS have general effects on RNA metabolism. We tested this hypothesis in a mouse model of ALS that is transgenic for a human disease-causing mutation in the enzyme superoxide dismutase 1 (SOD1). We analyzed RNA from laser-captured spinal cord motor neuron cell bodies of the mutant SOD1 strain, comparing the RNA profile with that from a corresponding wild-type SOD1 transgenic strain. We prepared the samples from animals that were presymptomatic, but which manifested abnormalities at the cellular level that are seen in ALS, including aggregation of the mutant protein in motor neuron cell bodies and defective morphology of neuromuscular junctions, the connections between neuron and muscle. We observed only minor changes in the level and splicing of RNA in the SOD1 mutant animals as compared with wild-type, suggesting that mutant SOD1 produces the toxic effects of ALS by a mechanism that does not involve global RNA disturbance. RNA-Seq of laser microdissection of motor neuron bodies from two biological replicates each of SOD1 YFP (wildtype 592) and SOD1 G85R YFP (737) transgenic mice.
2012-12-04 | E-GEOD-38820 | biostudies-arrayexpress
Project description:Amyotrophic Lateral Sclerosis (ALS) results from the selective and progressive degeneration of motor neurons. Although the underlying disease mechanisms remain unknown, glial cells have been implicated in ALS disease progression. Here we examine the effects of glial cell/motor neuron interactions on gene expression, using the hSOD1G93A mouse model of ALS. We detect striking cell autonomous and non-autonomous changes in gene expression in co-cultured motor neurons and glia, revealing that the two cell types profoundly affect each other. In addition, we found a remarkable concordance between the cell culture data, expression profiles of whole spinal cords, and of acutely isolated spinal cord cells, during disease progression in the G93A mouse model, providing validation of the cell culture approach. Bioinformatics analyses identified changes in the expression of specific genes and signaling pathways that may contribute to motor neuron degeneration in ALS, among which are TGF-b signaling pathways. RNA-seq profiles of: 1) 43 Sandwich culture samples at 3 different time points (3, 7 and 14 days), in duplicate, in different combinations of genetic background WT/SOD1_G93A mutant glia and WT/SOD1_G93A mutant neurons; 2) 16 spinal cord samples at 4 different time points, WT and SOD1_G93A mutant.
2013-02-11 | E-GEOD-43879 | biostudies-arrayexpress
Project description:Amyotrophic Lateral Sclerosis (ALS) results from the selective and progressive degeneration of motor neurons. Although the underlying disease mechanisms remain unknown, glial cells have been implicated in ALS disease progression. Here we examine the effects of glial cell/motor neuron interactions on gene expression, using the hSOD1G93A mouse model of ALS. We detect striking cell autonomous and non-autonomous changes in gene expression in co-cultured motor neurons and glia, revealing that the two cell types profoundly affect each other. In addition, we found a remarkable concordance between the cell culture data, expression profiles of whole spinal cords, and of acutely isolated spinal cord cells, during disease progression in the G93A mouse model, providing validation of the cell culture approach. Bioinformatics analyses identified changes in the expression of specific genes and signaling pathways that may contribute to motor neuron degeneration in ALS, among which are TGF-b signaling pathways.
2013-02-11 | GSE43879 | GEO
Project description:Motor-neuron specific microRNA-218 (miR-218) was recently put in the spotlight because of its striking roles in mouse development. However, miR-218 relevance to human motor neuron disease was not yet explored. Here, we demonstrate by neuropathology that miR-218 is abundant in healthy human motor neurons. However, in amyotrophic lateral sclerosis (ALS) motor neurons miR-218 is downregulated and its mRNA targets are reciprocally upregulated (de-repressed). We further identify the potassium channel Kv10.1 as a new miR-218 direct target that controls neuronal activity. In addition, we screened thousands of ALS genomes and identified six rare variants in the human miR-218-2 sequence. Intriguingly, miR-218 gene variants fail to regulate neuron activity, suggesting the importance of this small endogenous RNA for neuronal robustness. The underlying mechanisms involve inhibition of miR-218 biogenesis and reduced processing by DICER. Therefore, miR-218 activity uncovers a previously unappreciated facet of motor neuron specificity that may be particularly susceptible to failure in human ALS, contributes to a view of ALS as a disease with a prominent RNA component and suggests that miR-218 is a potential therapeutic target for motor neuron disease.
2019-08-28 | GSE136409 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the degeneration of upper and lower motor neurons leading to progressive muscle weakness, wasting and paralysis that result in death within a few years from disease onset.
In order to characterize RNA alterations in ALS, total RNAseq was performed in the ALS motor cortex, which is an early and vulnerable region in ALS.
| EGAS00001004286 | EGA