Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A Novel Microglia-Specific Transcriptional Signatures Correlates with Behavioural Deficits in Neuropsychiatric Lupus (NP-SLE)

ABSTRACT: Systemic lupus erythematosus (SLE) can present with neuropsychiatric manifestations, collectively termed NP-SLE. This study identifies a microglia-specific transcriptional signature in mouse models of NP-SLE. Through RNA-seq analysis of microglia and brain-infiltrating macrophages, we uncover an 18-gene 'NP-SLE signature' and its correlation with behavioral deficits. We also observe enrichment of genes associated with disease-associated microglia (DAM), which have been implicated in neurodegenerative diseases. These findings suggest a critical role for microglia-intrinsic mechanisms in the onset of NP-SLE and provide new insights into the cellular and molecular pathways driving this disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE288261 | GEO | 2025/02/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other
	GSE288261_CReCOM_Macrophage_CPM.csv.gz	Csv
	GSE288261_CReCOM_Macrophage_counts.csv.gz	Csv
	GSE288261_CReCOM_Microglia_CPM.csv.gz	Csv
	GSE288261_CReCOM_Microglia_counts.csv.gz	Csv

Items per page:

1 - 5 of 5

Similar Datasets

Behavioral Deficits Are Accompanied by Immunological and Neurochemical Changes in a Mouse Model for Neuropsychiatric Lupus (NP-SLE).

Project description:Neuropsychiatric symptoms of systemic lupus erythematosus (NP-SLE) have been understudied compared to end-organ failure and peripheral pathology. Neuropsychiatric symptoms, particularly affective and cognitive indications, may be among the earliest manifestations of SLE. Among the potential pathophysiological mechanisms responsible for NP-SLE are increased peripheral pro-inflammatory cytokines, subsequent induction of indoleamine-2,3-dioxygenase (IDO) and activation of the kynurenine pathway. In the MRL/MpJ-Faslpr (MRL/lpr) murine model of lupus, depression-like behavior and cognitive dysfunction is evident before significant levels of autoantibody titers and nephritis are present. We examined the behavioral profile of MRL/lpr mice and their congenic controls, a comprehensive plasma cytokine and chemokine profile, and brain levels of serotonin and kynurenine pathway metabolites. Consistent with previous studies, MRL/lpr mice had increased depression-like behavior and visuospatial memory impairment. Plasma levels of different inflammatory molecules (Haptoglobin, interleukin 10 (IL-10), interferon γ-inducible protein 10 (IP-10/CXCL10), lymphotactin, macrophage inhibitory protein 3β (MIP-3β/CCL19), monocyte chemotactic protein 1, 3 and 5 (MCP-1/CCL2, MCP-3/CCL7, MCP-5/CCL12), vascular cell adhesion molecule 1 (VCAM-1), lymphotactin and interferon γ (IFN-γ)) were increased in MRL/lpr mice. In cortex and hippocampus, MRL/lpr mice had increased levels of kynurenine pathway metabolites (kynurenine, 3-hydroxykynurenine, 3-hydroxynthranilic acid and quinolinic acid). Therefore, our study suggests that increased cytokine expression may be critical in the regulation subtle aspects of brain function in NP-SLE via induction of IDO and tryptophan/kynurenine metabolism.

| S-EPMC4519892 | biostudies-literature

SLE and atherosclerosis CD4+ T-cell RNAsequencing

Project description:Bulk RNAsequencing of CD4+ T-cells in SLE patients with (SLE-P) and without (SLE-NP) subclinical atherosclerotic plaques in carotid and femoral arteries, scanned by vascular ultrasound.

2024-10-10 | E-MTAB-13443 | biostudies-arrayexpress

SLE and atherosclerosis CD8+ T-cell RNAsequencing

Project description:Bulk RNAsequencing of CD8+ T-cells in SLE patients with (SLE-P) and without (SLE-NP) subclinical atherosclerotic plaques in carotid and femoral arteries, scanned by vascular ultrasound.

2024-10-10 | E-MTAB-13444 | biostudies-arrayexpress

Microglia from a SLE models

Project description:Microglia from a SLE models

| PRJNA1090481 | ENA

Microglia from a SLE models

Project description:We isolated CD45+CD11b+ microglia from mouse models of SLE and their respective controls.

2024-04-25 | GSE262152 | GEO

Project description:NP Metagenome

| PRJNA724020 | ENA

IKBKE contributes to neuropsychiatric manifestations in lupus-prone mice

Project description:Objectives. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multi-organ dysfunction. Neuropsychiatric SLE (NPSLE) occurs in 30~40% of patients with lupus and is the most severe presentation of SLE, frequently resulting in limitation of daily life. Recent studies have shown that microglia, tissue-resident macrophages in the central nervous system, are involved in the pathogenesis of NPSLE. Herein, we explored new therapeutic targets for NPSLE focusing on microglia. Methods. RNA sequencing of microglia in MRL/lpr, lupus-prone mice, as well as that of microglia cultured in vitro with cytokines were performed. A candidate gene, which could be a therapeutic target for NPSLE, was identified and its role on microglial activation and phagocytosis was investigated using specific inhibitors and siRNA. The effect of intracerebroventricular administration of the inhibitor on the behavioural abnormalities of MRL/lpr was also evaluated. Results. Transcriptome analysis revealed the upregulation of Ikbke, which encodes the inhibitor of nuclear factor kappa-B kinase epsilon (IKBKE) in both microglia from MRL/lpr mice and cytokine-stimulated microglia in vitro. Intracerebroventricular administration of an IKBKE inhibitor ameliorated cognitive function and suppressed microglial activation in MRL/lpr mice. Mechanistically, IKBKE inhibition reduced glycolysis, which dampened microglial activation and phagocytosis. Conclusions. These findings suggest that IKBKE plays a vital role in the pathogenesis of NPSLE via microglial activation, and it could serve as a therapeutic target for NPSLE.

2022-09-13 | GSE199662 | GEO

RNA Sequencing Facilitates Quantitative Analysis of Wild Type(MRL-mpj) and MRL-lpr (PBS or MSC treated) Hippocampoal Transcriptomes

Project description:Up to 75% of systematic lupus erythematosus (SLE) patients experience neuropsychiatric (NP) symptoms, called neuropsychiatric SLE (NPSLE), yet the underlying mechanisms remain elusive. Complement cascades mediate synaptic pruning by microglia during early postnatal brain development. The process in NPSLE remains unclear. Here, we show that complement-coordinated elimination of synaptic terminals participated in NPSLE in MRL/lpr mice, a lupus-prone murine model. We elucidated that lupus mice developed increased anxiety-like behaviors and persistent phagocytic microglia reactivation before overt peripheral lupus pathology. Microglial engulfment of synapses explained behavioral disorders. We further determined that neuronal Nr4a1 signaling was essential for attracting C1q synaptic deposition then apposition of phagocytic microglia, ensuing synaptic loss and neurological disease. Minocycline-deactivated microglia, antibody-blocked C1q, or neuronal Nr4a1 restore protected lupus mice from synapse loss and NP manifestations. Our findings revealed an active role of neurons in coordinating microglia-mediated synaptic loss and highlight neuronal Nr4a1 and C1q as critical components amenable to pharmacological intervention.

2022-02-23 | GSE154288 | GEO

NP-18 vs. NP-18AR transcriptional profile upon treatment with TK/GCV

Project description:Pancreatic cancer-derived cells NP-18 underwent four rounds of treatment with increasing doses of an adenoviral vector encoding TK enzyme and GCV. Surviving cells were termed NP-18AR and displayed decreased sensitivity to treatment. This experiment analyses the transcriptomic effect of TK/GCV treatment on NP-18AR as compared to that of NP-18 cells. Two-condition experiment, where response to treatment in naïve cells (NP-18) was compared to response to treatment in previously treated resistant cells (NP-18AR). Biological replicates: samples from 3 independently generated and independently treated NP-18AR lines (NP-18AR1, NP-18AR2 and NP-18AR3) were hibridized with 3 independently treated samples of NP-18 cells. A total of 9 hybridizations were performed, 2 for NP-18AR1 (including 1 dye-swap), 4 for NP-18AR2 (including 2 dye swaps) and 3 for NP-18AR3 (including 1 dye-swap).

2010-07-16 | E-GEOD-17137 | biostudies-arrayexpress

NP-18 vs. NP-18AR transcriptional profile upon treatment with TK/GCV

2010-07-16 | GSE17137 | GEO