Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

106 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional profiling in microglia and peripheral macrophages phenotypes during development and neuroinflammation in mouse

ABSTRACT: Understanding the respective role of microglia and infiltrating monocytes in neuroinflammatory conditions has recently seemed possible by the identification of a specific microglia signature. Here instead we provide evidence that peripheral macrophages may express some of the most commonly described microglia markers at some developmental stages or pathological conditions, in particular during chronic neuroinflammation. Further, our data support the hypothesis about phenotypic plasticity and convergence among distinct myeloid cells so that they may act as a functional unit rather than as different entities, boosting their mutual functions in different phases of disease. This holds relevant implications in the view of the growing use of myeloid cell therapies to treat brain disease in humans.

ORGANISM(S): Mus musculus

SUBMITTER: Ramesh Menon

PROVIDER: E-MTAB-8059 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Microglial expression of CD83 governs cellular activation and restrains autoimmune neuroinflammation

Project description:Microglial activation during neuroinflammation is crucial for coordinating the immune response against neuronal tissue and the initial response of microglia determines the severity of neuroinflammatory diseases. CD83 has been associated with early activation of microglia in various disease settings albeit its functional relevance for microglial biology was still elusive. Thus, we conducted a thorough assessment of CD83 regulation in microglia as well as its impact on microglial mediated neuroinflammation. Here, we describe for the first time that CD83 expression in microglia is not only associated with cellular activation but also with pro-resolving functions. Conditional deletion of CD83 causes malfunctioning responses to myelin debris, which results in an over-activated state during autoimmune neuroinflammation. Subsequently, CD83-deficient microglia recruit more pathogenic immune cells to the central nervous system and deteriorate resolving mechanism, which exacerbates the disease. Thus, CD83 in microglia orchestrates cellular activation and consequently, also resolution of neuroinflammation.

2023-06-28 | GSE230753 | GEO

Transcriptional profiling in macrophages in stimulated and unstimulated conditions.

Project description:Transcriptomes from macrophages at three stages were examined: a) Non-stimulated, b)Stimulated by Interleukin 4, c)Stimulated by LPS and Interferon gamma. Four biological replicate of each experiment were performed.

2018-05-31 | E-MTAB-6416 | biostudies-arrayexpress

Trancriptional profiling in microvesicles in stimulated (M1 and M2) and unstimulated conditions

Project description:Extracellular membrane vesicles (MVs) are powerful biomarkers in several pathological processes. The potential advantage of MVs relays on the assumption that their content reflects processes ongoing in pathologically relevant cell types. Using microarrays, we performed transcriptional profiling in stimulated (M1 and M2) and unstimulated conditions.

2016-06-03 | E-MTAB-1540 | biostudies-arrayexpress

RNA-Seq of human primary microglial cells treated with vehicle or human paired helical filaments (PHFs) purified from human tauopathy autopsy brain

Project description:Neuroinflammation is one of the major neuropathological hallmarks of Alzheimer's disease (AD) and related tauopathies. Activated microglia often co-exist in the same brain regions where tau protein accumulates as hyperphosphorylated and aggregated PHFs or neurofibrillary tangles (NFTs) within neurons in patients with AD and related tauopathies. However, the exact mechanisms how pathological tau could induce neuroinflammatory responses are not clear. In this study, we treated primary human microglia with purified human PHFs and performed RNA-sequence analysis.

2021-09-16 | E-MTAB-5742 | biostudies-arrayexpress

Gene expression changes in LPS-induced neuroinflammation

Project description:Neuroinflammation plays a role in the progression of several neurodegenerative disorders. We used a lipolysaccharide (LPS) model of neuroinflammation to characterize the gene expression changes underlying the inflammatory and behavioral effects of neuroinflammation. A single intracerebroventricular injection of LPS (5 ug) was administered into the lateral ventricle of mice and, 24 hours later, we examined gene expression in the cerebral cortex and hippocampus using microarray technology. Gene Ontology (GO) terms for inflammation and the ribosome were significantly enriched by LPS, whereas GO terms associated with learning and memory had decreased expression. We detected 224 changed transcripts in the cerebral cortex and 170 in the hippocampus. Expression of Egr1 (also known as Zif268) and Arc, two genes associated with learning and memory, was significantly lower in the cortex, but not hippocampus, of LPS-treated animals. Overall, altered expression of these genes may underlie some of the inflammatory and behavioral effects of neuroinflammation. Mice were given intracerebroventricular injections of saline vehicle (n = 4) or lipopolysaccharide (n = 4). Twenty-four hours later, we dissected the hippocampus and cerebral cortex and processed the tissue for microarray analysis. Gene expression changes observed in the microaray data were validated with quantitative real-time PCR.

2008-11-01 | E-GEOD-12284 | biostudies-arrayexpress

Transcriptionnal coregulator GRIP1 differentially modulate myeloid cell-driven neuroinflammation and response to IFN-beta therapy

Project description:Growing evidence are showing a pivotal role of macrophages (MФ) and microglia (MG) in the pathogenesis of Multiple sclerosis (MS). Interferon β (IFN β) and glucocorticoids are front line treatments in MS, and disrupting either type I IFN or GC receptor (GR) pathway in mice aggravates EAE, the mouse model of MS. Here, we evaluated GR Interacting Protein 1 actions in neuroinflammation by subjecting mice conditionally lacking GRIP1 in myeloid cells (cKO) to EAE. We showed that myeloid GRIP1 plays a dual role by promoting the ‘effector’ neuroinflammatory phase of EAE as well as mediating IFN β therapeutic effect. Our sorted MФ/MG transcriptome analysis reveals dramatic changes in inflammatory and IFN-pathway gene expression including potential differences of GRIP1 function in these distinct myeloid cell populations.

2020-10-03 | GSE141721 | GEO

Cannabinoid receptor 2 deficiency results in reduced neuroinflammation in an Alzheimer’s disease mouse model.

Project description:Several studies have indicated that the cannabinoid receptor 2(CB2) plays an important role in neuroinflammation associated with Alzheimer’s disease (AD) progression. The present study examined the role of CB2 in microglia activation in vitro as well as characterizing the neuroinflammatory process in a transgenic mouse model ofAD (APP/PS1mice). We demonstrate that microglia harvested from CB2-/- mice were less responsive to pro-inflammatory stimuli than CB2+/+ microglia based on the cell surface expression of ICAM and CD40 and the release of chemokines and cytokines CCL2, IL-6, and TNFα. Transgenic APP/PS1 mice lacking CB2showed reduced percentages of microglia and infiltrating macrophages. Furthermore, they showed lowered expression levels of pro-inflammatory chemokines and cytokine in the brain, as well as diminished concentrations of soluble Aβ 40/42.The reduction in neuroinflammation did not affect spatial learning and memory in APP/PS1*CB2-/- mice. These data suggest a role for the CB2 in Alzheimer’s disease-associated neuroinflammation independent of influencing Aβ mediated pathology and cognitive impairment.

2017-01-09 | GSE60903 | GEO

Microglial 25-hydroxycholesterol mediates neuroinflammation and neurodegeneration in a tauopathy mouse model.

Project description:Alzheimer’s disease (AD) is characterized by amyloid plaques and neurofibrillary tangles in addition to neuroinflammation and changes in brain lipid metabolism. Recent findings have demonstrated that microglia are key drivers of neurodegeneration in tauopathy mouse models. A subset of microglia referred to as disease-associated microglia (DAM) display gene signatures signifying changes in proinflammatory signaling and lipid metabolism in mouse models of amyloid and tau pathology. Ch25h is a DAM gene encoding cholesterol 25-hydroxylase that produces 25-hydroxycholesterol (25HC), a known modulator of inflammation as well as lipid metabolism. However, whether Ch25h influences tau-mediated neuroinflammation and neurodegeneration is unknown. Here, we show that in the absence of Ch25h and 25HC there is strikingly reduced age-dependent neurodegeneration and neuroinflammation in the hippocampus and entorhinal/piriform cortex of PS19 mice which express the P301S mutant human tau transgene. Transcriptomic analyses of bulk hippocampal tissue and single nuclei revealed that Ch25h deficiency in PS19 mice strongly suppressed proinflammatory cytokine and chemokine signaling in microglia and restored sterol synthesis. Our results suggest a key role for Ch25h/25HC in potentiating proinflammatory signaling to promote tau-mediated neurodegeneration. Ch25h may represent a novel therapeutic target for primary tauopathies, AD, and other neuroinflammatory diseases.

2023-12-08 | GSE242896 | GEO

Astrocyte-targeting therapy rescues cognitive impairment caused by neuroinflammation via the Nrf2 pathway (ChIP-Seq)

Project description:Neuroinflammation is a common feature of neurodegenerative disorders such as Alzheimer's disease (AD). Neuroinflammation is induced by dysregulated glial activation, and astrocytes, the most abundant glial cells, become reactive upon neuroinflammatory cytokines released from microglia, and actively contribute to neuronal loss. Therefore, blocking reactive astrocyte functions is a viable strategy to manage neurodegenerative disorders. However, factors or therapeutics directly regulating astrocyte subtype remain unexplored. Here, we identified transcription factor NF-E2-related factor 2 (Nrf2) as a therapeutic target in neurotoxic reactive astrocytes upon neuroinflammation. We found that the absence of Nrf2 promoted the activation of reactive astrocytes in the brain tissue samples obtained from AD model 5xFAD mice, whereas enhanced Nrf2 expression blocked the induction of reactive astrocyte gene expression by counteracting NF-kB subunit p65 recruitment. Neuroinflammatory astrocytes robustly upregulated genes associated with type I interferon and the antigen-presenting pathway, which were suppressed by Nrf2 pathway activation. Moreover, impaired cognitive behaviors observed in AD mice were rescued upon ALGERNON2 treatment, which potentiated Nrf2 pathway and reduced the induction of neurotoxic reactive astrocytes. Thus, we highlight the potential of astrocyte-targeting therapy by promoting the Nrf2 pathway signaling for neuroinflammation-triggered neurodegeneration.

2023-08-07 | GSE237423 | GEO

Cholesterol 25-hydroxylase mediates neuroinflammation and neurodegeneration in a mouse model of tauopathy

Project description:Alzheimer’s disease (AD) is characterized by amyloid plaques and neurofibrillary tangles in addition to neuroinflammation and changes in brain lipid metabolism. Recent findings have demonstrated that microglia are key drivers of neurodegeneration in tauopathy mouse models. A subset of microglia referred to as disease-associated microglia (DAM) display gene signatures signifying changes in proinflammatory signaling and lipid metabolism in mouse models of amyloid and tau pathology. Ch25h is a DAM gene encoding cholesterol 25- hydroxylase that produces 25-hydroxycholesterol (25HC), a known modulator of inflammation as well as lipid metabolism. However, whether Ch25h influences tau-mediated neuroinflammation and neurodegeneration is unknown. Here, we show that in the absence of Ch25h and the resultant reduction in 25HC there is strikingly reduced age-dependent neurodegeneration and neuroinflammation in the hippocampus and entorhinal/piriform cortex of PS19 mice, which express the P301S mutant human tau transgene. Transcriptomic analyses of bulk hippocampal tissue and single nuclei revealed that Ch25h deficiency in PS19 mice strongly suppressed proinflammatory cytokine and chemokine signaling in microglia and restored sterol synthesis. Our results suggest a key role for Ch25h/25HC in potentiating proinflammatory signaling to promote tau-mediated neurodegeneration. Ch25h may represent a novel therapeutic target for primary tauopathies, AD, and other neuroinflammatory diseases.

2024-02-23 | GSE250277 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data