TNFR2 signaling regulates the immunomodulatory function of oligodendrocyte precursor cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA748767 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15210606.fastq.gz | Fastqsanger.gz | |||
| SRR15210607.fastq.gz | Fastqsanger.gz | |||
| SRR15210608.fastq.gz | Fastqsanger.gz | |||
| SRR15210609.fastq.gz | Fastqsanger.gz | |||
| SRR15210610.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Multiple sclerosis (MS) is a neuroimmune disorder characterized by inflammation, CNS demyelination, and progressive neurodegeneration. Chronic MS patients exhibit impaired remyelination capacity, partly due to the changes that oligodendrocyte precursor cells (OPCs) undergo in response to the MS lesion environment. The cytokine tumor necrosis factor (TNF) is present in the MS affected CNS and has been implicated in disease pathophysiology. Of the two active forms of TNF, transmembrane (tmTNF) and soluble (solTNF), tmTNF signals via TNFR2 mediating protective and reparative effects, including remyelination, whereas solTNF signals predominantly via TNFR1 promoting neurotoxicity. To better understand the mechanisms underlying repair failure in MS, we investigated the cellular responses of OPCs to inflammatory exposure and the specific role of TNFR2 signaling in their modulation. Following treatment of cultured OPCs with IFNg, IL1b and TNF we observed by RNA sequencing marked inflammatory and immune activation of OPCs, accompanied by metabolic changes and dysregulation of their proliferation and differentiation programming. We also established the high likelihood of cell-cell interaction between OPCs and microglia in neuroinflammatory conditions, with OPCs able to produce chemokines that can recruit and activate microglia. Importantly, we showed that these functions are exacerbated when TNFR2 is ablated. Together, our data indicate that neuroinflammation leads OPCs to shift towards an immunomodulatory phenotype while diminishing their capacity to proliferate and differentiate, thus impairing their repair function. Furthermore, we demonstrated that TNFR2 plays a key role in this process, suggesting that boosting TNFR2 activation or its downstream signals could be an effective strategy to restore OPC reparative capacity in demyelinating disease.
2021-07-28 | GSE180604 | GEO
Project description:Multiple sclerosis (MS) is a neuroimmune disorder characterized by inflammation, CNS demyelination, and progressive neurodegeneration. Chronic MS patients exhibit impaired remyelination capacity, partly due to the changes that oligodendrocyte precursor cells (OPCs) undergo in response to the MS lesion environment. The cytokine tumor necrosis factor (TNF) is present in the MS-affected CNS and has been implicated in disease pathophysiology. Of the two active forms of TNF, transmembrane (tmTNF) and soluble (solTNF), tmTNF signals via TNFR2 mediating protective and reparative effects, including remyelination, whereas solTNF signals predominantly via TNFR1 promoting neurotoxicity. To better understand the mechanisms underlying repair failure in MS, we investigated the cellular responses of OPCs to inflammatory exposure and the specific role of TNFR2 signaling in their modulation. Following treatment of cultured OPCs with IFNγ, IL1β, and TNF, we observed, by RNA sequencing, marked inflammatory and immune activation of OPCs, accompanied by metabolic changes and dysregulation of their proliferation and differentiation programming. We also established the high likelihood of cell-cell interaction between OPCs and microglia in neuroinflammatory conditions, with OPCs able to produce chemokines that can recruit and activate microglia. Importantly, we showed that these functions are exacerbated when TNFR2 is ablated. Together, our data indicate that neuroinflammation leads OPCs to shift towards an immunomodulatory phenotype while diminishing their capacity to proliferate and differentiate, thus impairing their repair function. Furthermore, we demonstrated that TNFR2 plays a key role in this process, suggesting that boosting TNFR2 activation or its downstream signals could be an effective strategy to restore OPC reparative capacity in demyelinating disease.
| S-EPMC8306473 | biostudies-literature
Project description:Astrocytes participate in synaptic transmission and plasticity through tightly regulated, bidirectional communication with neurons, both pre- and post-synaptic elements, as well as microglia and oligodendrocytes. A key component of astrocyte-mediated synaptic regulation is the cytokine tumor necrosis factor (TNF). TNF signals via two cognate receptors, TNFR1 and TNFR2, both expressed in astrocytes. While TNFR1 signaling in astrocytes has been long demonstrated to be necessary for physiological synaptic function, the role of astroglial TNFR2 has never been explored. Here, we demonstrate that astroglial TNFR2 is essential for maintaining hippocampal synaptic function and plasticity in physiological conditions. Indeed, GfapcreERT2:Tnfrsf1bfl/fl mice with selective ablation of TNFR2 in astrocytes exhibited dysregulated expression of neuronal and glial proteins (e.g. SNARE complex molecules, glutamate receptor subunits, glutamate transporters) essential for hippocampal synaptic transmission and plasticity. Hippocampal astrocytes sorted from GfapcreERT2:Tnfrsf1bfl/fl mice displayed downregulation of genes and pathways implicated in synaptic plasticity, astrocyte-neuron and astrocyte-oligodendrocyte communication. These alterations were accompanied by increased glial reactivity and impaired astrocyte calcium dynamics, and ultimately translated into functional deficits, specifically impaired long-term potentiation (LTP) and cognitive functions. Notably, male GfapcreERT2:Tnfrsf1bfl/fl mice exhibited more pronounced hippocampal synaptic and cellular alterations, suggesting sex-dependent differences in astroglial TNFR2 regulation of synaptic function. Together, these findings indicate that TNFR2 signaling in astrocytes is essential for proper astrocyte-neuron communication at the basis of synaptic function, and that this is regulated in a sex-dependent manner.
2025-08-01 | GSE288931 | GEO
Project description:Oligodendrocytes, the myelinating cells of the central nervous system, are essential for correct brain function. They originate from oligodendrocyte precursor cells (OPCs) through a differentiation process which is only incompletely understood and impaired in a variety of demyelinating diseases. Better knowledge of this differentiation holds the promise to develop novel therapies for these disorders. We investigated the differentiation of rat oligodendrocyte precursor cells to oligodendrocytes in vitro. After confirmation of differentiation by immunohistochemical analysis using cell type-specific marker proteins, we conducted a quantitative proteomics study using tandem mass tags (TMT). We investigated four time points of differentiation covering early, intermediate, and late stages. Data analysis was perfomed using Mascot and Maxquant.
2019-06-21 | PXD012544 | Pride
Project description:Oligodendrocyte precursor cells facilitate neuronal lysosome release
| PRJNA1207448 | ENA
Project description:Oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs). Chd7 is ATP-dependent chromatin-remodeling enzyme. We performed microarray analysis to examine changes in gene expression between control and Chd7 knockdown OPCs. Results provide insight into the function of Chd7 in oligodendrocyte development.
2018-03-01 | GSE95347 | GEO
Project description:Oligodendrocyte development is tightly controlled by extrinsic signals; however, mechanisms that modulate cellular responses to these factors remain unclear. Six-transmembrane glycerophosphodiester phosphodiesterases (GDEs) are emerging as central regulators of cellular differentiation via their ability to shed glycosylphosphatidylinositol (GPI)-anchored proteins from the cell surface. We show here that GDE3 controls the pace of oligodendrocyte generation by negatively regulating oligodendrocyte precursor cell (OPC) proliferation. GDE3 inhibits OPC proliferation by stimulating ciliary neurotrophic factor (CNTF)-mediated signaling through release of CNTFRα, the ligand-binding component of the CNTF-receptor multiprotein complex, which can function as a soluble factor to activate CNTF signaling. GDE3 releases soluble CNTFRα by GPI-anchor cleavage from the plasma membrane and from extracellular vesicles (EVs) after co-recruitment of CNTFRα in EVs. These studies uncover new physiological roles for GDE3 in gliogenesis and identify GDE3 as a key regulator of CNTF-dependent regulation of OPC proliferation through release of CNTFRα.
2019-09-06 | GSE135819 | GEO
Project description:GDE3 regulates oligodendrocyte precursor proliferation via release of soluble CNTFRα
| PRJNA560200 | ENA
Project description:Transcriptome outcome of rat oligodendrocyte precursor cells, which were knocked down with short-hairpin RNA (shRNA) for vascular cell adhesion molecule 1 (VCAM1)
2016-10-14 | GSE86862 | GEO
Project description:We report single cell gene expression analysis of human fetal and mouse postnatal oligodendrocyte precursor cells
2023-09-13 | GSE214086 | GEO