RNA-Seq profiling in PBMCs and spinal cord from ALS patients and healthy controls
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ABSTRACT:
PROVIDER: PRJNA474425 | ENA |
REPOSITORIES: ENA
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Project description:Amyotrophic lateral sclerosis (ALS) is a paralytic degenerative disease of the nervous system. In the SOD1 mouse model of ALS we found loss of the molecular and functional microglia signature associated with pronounced expression of miR-155 in SOD1 mice. We also found increased expression of miR-155 in the spinal cord of ALS subjects. Genetic ablation of miR-155 increased survival in SOD1 mice and reversed the abnormal microglial and monocyte molecular signature. In addition, dysregulated proteins in the spinal cord of SOD1 mice that we identified in human ALS spinal cords and CSF were restored in SOD1G93A/miR155-/- mice. Treatment of SOD1 mice with anti-miR-155 SOD1 mice injected systemically or into the cerebrospinal fluid prolonged survival and restored the microglial unique genetic and microRNA profiles. Our findings provide a new avenue for immune based therapy of ALS by targeting miR-155.
2014-11-24 | GSE52959 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) is a paralytic degenerative disease of the nervous system. In the SOD1 mouse model of ALS we found loss of the molecular and functional microglia signature associated with pronounced expression of miR-155 in SOD1 mice. We also found increased expression of miR-155 in the spinal cord of ALS subjects. Genetic ablation of miR-155 increased survival in SOD1 mice and reversed the abnormal microglial and monocyte molecular signature. In addition, dysregulated proteins in the spinal cord of SOD1 mice that we identified in human ALS spinal cords and CSF were restored in SOD1G93A/miR155-/- mice. Treatment of SOD1 mice with anti-miR-155 SOD1 mice injected systemically or into the cerebrospinal fluid prolonged survival and restored the microglial unique genetic and microRNA profiles. Our findings provide a new avenue for immune based therapy of ALS by targeting miR-155.
2014-11-24 | GSE52670 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) is a paralytic degenerative disease of the nervous system. In the SOD1 mouse model of ALS we found loss of the molecular and functional microglia signature associated with pronounced expression of miR-155 in SOD1 mice. We also found increased expression of miR-155 in the spinal cord of ALS subjects. Genetic ablation of miR-155 increased survival in SOD1 mice and reversed the abnormal microglial and monocyte molecular signature. In addition, dysregulated proteins in the spinal cord of SOD1 mice that we identified in human ALS spinal cords and CSF were restored in SOD1G93A/miR155-/- mice. Treatment of SOD1 mice with anti-miR-155 SOD1 mice injected systemically or into the cerebrospinal fluid prolonged survival and restored the microglial unique genetic and microRNA profiles. Our findings provide a new avenue for immune based therapy of ALS by targeting miR-155.
2014-11-24 | GSE52672 | GEO
Project description:Identification of amyotrophic lateral sclerosis (ALS) associated genes. Post mortem spinal cord grey matter from sporadic and familial ALS patients compared with controls.
2007-09-26 | E-GEOD-833 | biostudies-arrayexpress
Project description:Amyotrophic lateral sclerosis (ALS) is an incurable neurological disease featuring progressive loss of motor neuron (MN) function in the brain and spinal cord. Mutations in TARDBP, encoding the RNA-binding protein TDP-43, are one cause of ALS and TDP-43 mislocalization in MNs is a key pathological feature of >95% of ALS cases. While numerous studies support altered RNA regulation by TDP-43 as a major cause of disease, specific changes within MNs that trigger disease onset remain unclear. Here, we combined Translating Ribosome Affinity Purification (TRAP) with RNA sequencing to identify molecular changes in spinal MNs of TDP-43–driven ALS at motor symptom onset. By comparing the MN translatome of hTDP-43A315T mice to littermate controls and to mice expressing wildtype hTDP-43, we identify hundreds of mRNAs that were selectively up- or downregulated in MNs. We validated effects on Tex26, Syngr4, and Plekhb1 mRNAs in an independent TRAP experiment. Moreover, by quantitative immunostaining of spinal cord MNs we found corresponding protein level changes for SYNGR4 and PLEKHB1. We also observed these changes in spinal MNs of an independent ALS mouse model caused by a different patient mutant allele of TDP-43, suggesting that they may be a general feature of TDP-43-driven ALS. Thus, we have identified two new proteins deregulated in MNs at motor symptom onset in TDP-43-driven ALS models. This spatial and temporal pattern suggests that deregulation of these proteins could be functionally important for driving the transition to the symptomatic phase of disease.
2023-01-01 | GSE144640 | GEO
Project description:Transcripional profiling of lymphocytes from patients with amyotrophic lateral sclerosis (ALS) (n=11) and healthy control subjects (n=11). The goal was to determine disease response expression signatures relevant of ALS pathogenesis that affect brain and spinal cord. The reference design was used: each Cy5-labeled cRNA sample from ALS patient or healthy control subject was cohybridized on Agilent-014850 Whole Human Genome Microarray 4x44K G4112F with the reference pool formed with equal amounts of Cy3-labeled cRNAs from each sample from the healthy control group. Eleven lymphocyte samples from definite sporadic ALS patients and eleven samples from healthy control subjects were used.
2011-12-11 | E-GEOD-28253 | biostudies-arrayexpress
Project description:Transcripional profiling of lymphocytes from patients with amyotrophic lateral sclerosis (ALS) (n=11) and healthy control subjects (n=11). The goal was to determine disease response expression signatures relevant of ALS pathogenesis that affect brain and spinal cord. The reference design was used: each Cy5-labeled cRNA sample from ALS patient or healthy control subject was cohybridized on Agilent-014850 Whole Human Genome Microarray 4x44K G4112F with the reference pool formed with equal amounts of Cy3-labeled cRNAs from each sample from the healthy control group.
2011-12-11 | GSE28253 | GEO
Project description:Amyotrophic lateral sclerosis (ALS) is an incurable disease characterized by proteinaceous aggregate accumulation and neuroinflammation culminating in rapidly progressive lower and upper motor neuron death. To interrogate cell-intrinsic and inter-cell type perturbations in ALS, single-nucleus RNA sequencing was performed on the lumbar spinal cord in the murine ALS model SOD1G93A transgenic and littermate control mice at peri-symptomatic onset stage of disease, age 90 days. This work uncovered perturbed tripartite synapse functions, complement activation and metabolic stress in the affected spinal cord; processes evidenced by cell death and proteolytic stress-associated gene sets. Concomitantly, these pro-damage events in the spinal cord co-existed with dysregulated reparative mechanisms. This work provides a resource of cell-specific niches in the ALS spinal cord and asserts that interwoven dysfunctional neuronal-glial communications mediating neurodegeneration are underway prior to overt disease manifestation and are recapitulated, in part, in the human post-mortem ALS spinal cord.
2022-02-18 | GSE173524 | GEO
Project description:Coding and long non-coding RNA metabolism is now revealing its crucial role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. In this work, we performed Illumina RNA-seq analysis on Peripheral Blood Mononuclear Cells (PBMCs) from Sporadic and mutated ALS patients (mutations in FUS, TARDBP, SOD1, C9Orf72 and VCP genes) and healthy controls. Our aim is the whole-transcriptome characterization of PBMCs content, both in terms of coding and non coding RNAs, in order to compare the disease state to the healthy controls, both for sporadic patients and for mutated patients. Out dataset is a starting point for the omni-comprehensive analysis of coding and long non coding RNAs, from an easy to withdraw, manage and store tissue that shows to be a suitable model for RNA profiling in ALS.
2018-07-04 | GSE115259 | GEO
Project description:This project is "Phosphoproteomic analysis of the lumbar spinal cord, a lesion site in the amyotrophic lateral sclerosis (ALS) mouse model SOD1G93A mice". The aim of this study is to clarify the phosphorylation changes by the lumbar spinal cord of SOD1G93A mice at 20w by applying proteomics technology. The goal of this study is to better understand the pathogenesis of ALS. lumbar spinal cord of SOD1G93A mice (n=5) and WT mice (n=4) were collected at 20w, and the phosphoproteomics were compared.
2022-05-19 | PXD030651 | JPOST Repository