Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA399193 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5952441.fastq.gz | Fastqsanger.gz | |||
| SRR5952442.fastq.gz | Fastqsanger.gz | |||
| SRR5952443.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 3 of 3 |
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Project description:Neuronal EphB1 induces STAT3 activation in astrocytes, which is impaired in ALS models
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Project description:Neuronal EphB1 induces STAT3 activation in astrocytes, which is impaired in ALS models [Mm]
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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.
2017-09-01 | GSE102903 | GEO
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.
2017-09-01 | GSE102902 | GEO
Project description:This datased was used to obtain a genome-wide expression signature for the early response of mouse motor neurons to mutant SOD1 astrocytes conditioned media. Neurons, far from living in isolation, are surrounded by a host of other neuronal and non-neuronal cells, such as astrocytes. The latter entertain complex functional interactions with neighboring neurons, which, under normal conditions, are important for the their well-being. In pathological situations, however, altered astrocyte behavior may contribute to the demise of neighboring neurons. Such non-cell autonomous pathogenic scenario is increasingly considered in a variety of disorders, including amyotrophic lateral sclerosis (ALS), the most frequent adult-onset paralytic disorder. Assembly and interrogation of gene regulatory models has helped elucidate causal mechanisms responsible for the presentation of several tumor-related phenotypes. To systematically elucidate the effectors of neurodegeneration in a model of ALS, we first developed techniques for the efficient purification of motor neurons (MNs), the primary target of ALS neurodegenerative process. We then generated gene expression profiles to fully characterize the critical timepoints associated with initiation and commitment of MN degenerative progression in an in vitro murine mutant SOD1 (mSOD1) model of ALS. ES cells were derived from transgenic Hlxb9-GFP1Tmj mice expressing eGFP and CD2 driven by the mouse HB9 promoter. These cells were then differentiated into motor neurons (ES-MN) as described previously [PMID 12176325] ES-MN were exposed to non-transgenic (NTg), G93A mutant SOD1 (mSOD1) or wtSOD1 over-expression astrocytes conditioned media for 0 days (time zero control), 1 day, and 3 days. Total RNA was extracted and profiled by RNAseq.
2014-12-17 | E-GEOD-49023 | biostudies-arrayexpress
Project description:We analyzed the transcriptional profile of normal astrocytes and astrocytes made reactive by AAV gene transfer of a contitutive form of JAK2 (JAK2ca). We show that activation of the JAK2-STAT3 pathway by JAK2ca induces significant transcriptional changes in astrocytes, recapitulating several molecular hallmarks of reactivity
2022-06-29 | GSE107486 | GEO
Project description:Mechanisms underlying motor neuron degeneration in amyotrophic lateral sclerosis (ALS) are yet unclear. Specific deletion of the ER-component membralin in astrocytes manifested postnatal motor defects and lethality in mice, causing the accumulation of extracellular glutamate through reducing the glutamate transporter EAAT2. Restoring EAAT2 levels in membralin KO astrocytes limited astrocyte-dependent excitotoxicity in motor neurons. Transcriptomic profiles from mouse astrocytic membralin KO motor cortex indicateed significant perturbation in KEGG pathway components related to ALS, including downregulation of Eaat2 and upregulation of Tnfrsf1a. Changes in gene expression with membralin deletion also overlapped with mouse ALS models and reactive astrocytes. Our results shown that activation of TNF receptor (TNFR1)-NFkB pathway known to suppress Eaat2 transcription was upregulated with membralin deletion. Further, reduced membralin and EAAT2 levels correlated with disease progression in spinal cord from SOD1-mutant mouse models, and reductions in membralin/EAAT2 were observed in human ALS spinal cord. Importantly, overexpression of membralin in SOD1G93A astrocytes decreased TNFR1 levels and increased EAAT2 expression, and improved motor neuron survival. Importantly, upregulation of membralin in SOD1G93A mice significantly prolonged mouse survival. Together, our study provides a mechanism for ALS pathogenesis where membralin limits glutamatergic neurotoxicity, suggesting that modulating membralin has potential in ALS therapy
2019-05-07 | GSE130763 | GEO
Project description:Non-neuronal cells, including astrocytes, play a crucial role in the selective motor neuron pathology in amyotrophic lateral sclerosis (ALS). How astrocytes exactly contribute to the disease is not fully elucidated. Therefore, we characterised human induced pluripotent stem cell (hiPSC)-derived astrocytes from FUS-ALS patients, and incorporated these astrocytes into a human motor unit model to investigate the astrocytic effect on hiPSC-derived motor neuron network and neuromuscular junctions (NMJs). We observed a dysregulation of astrocyte homeostasis, which resulted in a FUS-ALS-mediated increase in reactivity and secretion of pro-inflammatory cytokines. Upon coculture with motor neurons and myotubes, we detected a cytotoxic effect on motor neuron-neurite morphology and outgrowth, as well as on NMJ formation and functionality, which was improved or fully rescued by isogenic control astrocytes. We conclude that mutant astrocytes have both a gain-of-toxicity and loss-of-support function in ALS, ultimately contributing to the disruption of motor neuron homeostasis, intercellular networks and NMJs.
2023-01-19 | GSE196219 | GEO
Project description:This datased was used to obtain a genome-wide expression signature for the early response of mouse motor neurons to mutant SOD1 astrocytes conditioned media. Neurons, far from living in isolation, are surrounded by a host of other neuronal and non-neuronal cells, such as astrocytes. The latter entertain complex functional interactions with neighboring neurons, which, under normal conditions, are important for the their well-being. In pathological situations, however, altered astrocyte behavior may contribute to the demise of neighboring neurons. Such non-cell autonomous pathogenic scenario is increasingly considered in a variety of disorders, including amyotrophic lateral sclerosis (ALS), the most frequent adult-onset paralytic disorder. Assembly and interrogation of gene regulatory models has helped elucidate causal mechanisms responsible for the presentation of several tumor-related phenotypes. To systematically elucidate the effectors of neurodegeneration in a model of ALS, we first developed techniques for the efficient purification of motor neurons (MNs), the primary target of ALS neurodegenerative process. We then generated gene expression profiles to fully characterize the critical timepoints associated with initiation and commitment of MN degenerative progression in an in vitro murine mutant SOD1 (mSOD1) model of ALS.
2014-12-17 | GSE49023 | GEO
Project description:Background: Microglia play crucial roles in mediating neuronal homeostasis but have been implicated in contributing to amyotrophic lateral sclerosis (ALS). However, the role of microglia in ALS remains incompletely understood. Methods: Here, we generated highly enriched cultures of VCP mutant microglia derived from human induced pluripotent stem cells (hiPSCs) to investigate their cell autonomous and non-cell autonomous roles in ALS pathogenesis. We used RNA-sequencing, proteomics and functional assays to study hiPSC derived VCP mutant microglia and their effects on hiPSC derived motor neurons and astrocytes. Results: Transcriptomic, proteomic and functional analyses revealed immune and lysosomal dysfunction in VCP mutant microglia. Stimulating healthy microglia with inflammatory inducer lipopolysaccharide (LPS) showed partial overlap with VCP mutant microglia in their reactive transformation. LPS-stimulated VCP mutant microglia displayed differential activation of inflammatory pathways compared with LPS-stimulated healthy microglia. Conserved gene expression changes were identified between VCP mutant microglia, SOD1 mutant mice microglia, and postmortem ALS spinal cord microglial signatures, including increased expression of the transmembrane glycoprotein GPNMB. While knockdown of GPNMB affected inflammatory and phagocytosis processes in microglia, this was not sufficient to ameliorate cell autonomous phenotypes in VCP mutant microglia. Secreted factors from VCP mutant microglia were sufficient to activate the JAK-STAT pathway in hiPSC derived motor neurons and astrocytes. Conclusions: VCP mutant microglia undergo cell autonomous reactive transformation involving immune and lysosomal dysfunction that partially recapitulate key phenotypes of microglia from ALS models and post mortem tissue and are independent of GPNMB. VCP mutant microglia elicit non cell autonomous responses in motor neurons and astrocytes involving the JAK-STAT pathway.
2024-12-09 | GSE282665 | GEO