CSF1R inhibition by PLX5622 affects multiple immune cell compartments with tissue-specific metabolic effects
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA783003 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17020800_1.fastq.gz | Fastqsanger.gz | |||
| SRR17020800_2.fastq.gz | Fastqsanger.gz | |||
| SRR17020801_1.fastq.gz | Fastqsanger.gz | |||
| SRR17020801_2.fastq.gz | Fastqsanger.gz | |||
| SRR17020802_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 52 |
Similar Datasets
Project description:We found that long-term CSF1R-inhibition by PLX5622 depleted tissue resident macrophages in different organs. This alteration resulted in a dual impact on glucose homeostasis with improved insulin sensitivity predominantly in the liver, combined with an insulin secretion defect in the islets of Langerhans. RNA-Seq analysis of islets of mice treated with PLX5622 compared to control mice hinted at a role of IL-1β in supporting insulin secretion,
2023-06-29 | GSE189434 | GEO
Project description:Microglia are the resident myeloid cell in the central nervous system (CNS). Like other terminally differentiated myeloid cells, microglia rely on Csf1r signaling for survival and maintenance. Surprisingly, a small subset of microglia in the murine brain can survive without Csf1r signaling, as shown in Csf1r KO mice as well as in mice that have been treated with Csf1r inhibitor PLX5622. The nature of such Csf1r independent microglial population has not been fully characterized. Here we applied single-cell RNA-seq to examine the remaining microglia in C57/BL6J mice that were treated with PLX5622 diet (1200 mg/kg, 14 days), which results >90% microglial removal.
2019-12-01 | GSE133773 | GEO
Project description:Microglia are the resident myeloid cell in the central nervous system (CNS). Like other terminally differentiated myeloid cells, microglia rely on Csf1r signaling for survival and maintenance. Surprisingly, a small subset of microglia in the murine brain can survive without Csf1r signaling, as shown in Csf1r KO mice as well as in mice that have been treated with Csf1r inhibitor PLX5622. The nature of such Csf1r independent microglial population has not been fully characterized. Here we applied single-cell RNA-seq to examine the remaining microglia in C57/BL6J mice that were treated with PLX5622 diet (1200 mg/kg, 14 days), which results >90% microglial removal.
2020-05-09 | GSE150169 | GEO
Project description:As the resident macrophages of the CNS, microglia fulfill manifold functions important for brain development and homeostasis. In the context of neurodegenerative diseases, they are crucial for de- and regenerative as well as immunological processes. The discovery of distinct activation patterns and increased phagocytosis indicated a damaging role of microglia in multiple system atrophy. This devastating, rapidly progressing atypical parkinsonian disorder is characterized by alpha-synuclein accumulation in the cytoplasm of oligodendrocytes. Alpha-synuclein aggregates have been related to myelin loss, severe neurodegeneration, and motor deficits accompanied by a region-specific myeloid immune response. Analyzing the gene expression profile of microglia in a mouse model of multiple system atrophy, MBP29-hα-syn mice, we identified a disease-assoctiated expression profile with an upregulation of the colony-stimulating factor 1 (Csf1). Thus, we hypothesized that targeting the CSF1 receptor using the small-molecule inhibitor PLX5622 reduces myeloid cells and thereby modifies the disease progression and neuropathological phenotype in this mouse model. After validation of a widespread depletion of myeloid cells after CSF1R inhibition, we consequently analyzed the survival, motor functions, neuropathological characteristics, and gene expression of affected brain regions in MBP29-hα-syn mice. Intriguingly, we identified a two-faced outcome comprising (1) an improved survival rate (24%) accompanied by delayed onset of neurological symptoms in contrast to (2) severely impaired motor functions in beam walking, pole test, and RotaRod of PLX5622-treated MBP29-hα-syn mice. Gene expression analysis revealed that PLX5622 reversed myeloid cell activation, however, predominantly reduced the expression of genes related to transsynaptic signaling and signal release. While these transcriptional changes were accompanied by a reduction of dopaminergic neurons in the substantia nigra pars compacta (19%) of PLX5622-treated MBP29-hα-syn mice, an increase of the striatal neuritic density was observed without changes in alpha-synuclein levels or myelin lipids in the forebrain. Together, our findings provide insight into the complex role of myeloid cell depletion in multiple system atrophy by demonstrating a two-faced outcome on the behavioral and neuronal phenotype of MBP29-hα-syn mice. Therefore, it is important to carefully balance the beneficial and adversive effects of CSF1R inhibition in different models of neurodegenerative disorders prior to clinical translation.
2022-08-01 | GSE197153 | GEO
Project description:As the elderly population grows, chronic metabolic dysfunction including obesity and diabetes are becoming increasingly common comorbidities. Hypothalamic inflammation through CNS resident microglia serves as a common pathway between developing obesity and developing systemic aging pathologies. Despite understanding aging as a life-long process involving interactions between individuals and their environment, limited studies address the dynamics of environment interactions with aging or aging therapeutics. We previously demonstrated environmental enrichment (EE) is an effective model for studying improved metabolic health and overall healthspan in mice, which acts through a brain-fat axis. Here we investigated the CSF1R inhibitor PLX5622 (PLX), which depletes microglia, and its effects on metabolic decline in aging in interaction with EE. PLX in combination with EE substantially improved metabolic outcomes in middle-aged female mice over PLX or EE alone. Chronic PLX treatment depleted 75% of microglia from the hypothalamus and reduced markers of inflammation without affecting brain-derived neurotrophic factor levels induced by EE. Adipose tissue remodeling and adipose tissue macrophage modulation were observed in response to CSF1R inhibition, which may contribute to the combined benefits seen in EE with PLX. Our study suggests benefits exist from combined drug and lifestyle interventions in aged animals.
| S-EPMC7041757 | biostudies-literature
Project description:Hematogenous macrophages infiltrate the brain after virus infection. We use a CSF1R inhibitior, PLX5622 to deplete microglia from the brain. However, macrophages also express the CSF1R and may be affected by PLX5622-treatment of mice.
2018-02-28 | GSE103379 | GEO
Project description:Microglia are resident immune cells of the central nervous system, yet their functions far exceed those related to immunology. From pruning neural synapses during development to preventing excessive neural activity throughout life, microglia are intimately involved in the brain’s most basic processes. Studies have reported a close interaction between microglia and endothelial cells, as well as both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, much less work has been done to understand microglia-endothelial cell interactions in the healthy brain. Here, we aim to determine the role of microglia at the healthy BBB. We used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia and analyzed BBB ultrastructure, permeability, and transcriptome. Interestingly, we found that, despite their direct contact with endothelial cells, microglia are not necessary for maintenance of BBB structure, function, or gene expression in the healthy brain. However, we found that PLX5622 treatment alters brain endothelial cholesterol metabolism, and this effect was independent from microglial depletion, suggesting PLX5622 has off-target effects on brain vasculature.
2024-05-22 | GSE267590 | GEO
Project description:Microglia are resident immune cells of the central nervous system, yet their functions far exceed those related to immunology. From pruning neural synapses during development to preventing excessive neural activity throughout life, microglia are intimately involved in the brain’s most basic processes. Studies have reported a close interaction between microglia and endothelial cells, as well as both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, much less work has been done to understand microglia-endothelial cell interactions in the healthy brain. Here, we aim to determine the role of microglia at the healthy BBB. We used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia and analyzed BBB ultrastructure, permeability, and transcriptome. Interestingly, we found that, despite their direct contact with endothelial cells, microglia are not necessary for maintenance of BBB structure, function, or gene expression in the healthy brain. However, we found that PLX5622 treatment alters brain endothelial cholesterol metabolism, and this effect was independent from microglial depletion, suggesting PLX5622 has off-target effects on brain vasculature.
2024-05-22 | GSE267594 | GEO
Project description:Microglia are resident immune cells of the central nervous system, yet their functions far exceed those related to immunology. From pruning neural synapses during development to preventing excessive neural activity throughout life, microglia are intimately involved in the brain’s most basic processes. Studies have reported a close interaction between microglia and endothelial cells, as well as both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, much less work has been done to understand microglia-endothelial cell interactions in the healthy brain. Here, we aim to determine the role of microglia at the healthy BBB. We used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia and analyzed BBB ultrastructure, permeability, and transcriptome. Interestingly, we found that, despite their direct contact with endothelial cells, microglia are not necessary for maintenance of BBB structure, function, or gene expression in the healthy brain. However, we found that PLX5622 treatment alters brain endothelial cholesterol metabolism, and this effect was independent from microglial depletion, suggesting PLX5622 has off-target effects on brain vasculature.
2024-05-22 | GSE267592 | GEO
Project description:Microglia are resident immune cells of the central nervous system, yet their functions far exceed those related to immunology. From pruning neural synapses during development to preventing excessive neural activity throughout life, microglia are intimately involved in the brain’s most basic processes. Studies have reported a close interaction between microglia and endothelial cells, as well as both helpful and harmful roles for microglia at the blood-brain barrier (BBB) in the context of disease. However, much less work has been done to understand microglia-endothelial cell interactions in the healthy brain. Here, we aim to determine the role of microglia at the healthy BBB. We used the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia and analyzed BBB ultrastructure, permeability, and transcriptome. Interestingly, we found that, despite their direct contact with endothelial cells, microglia are not necessary for maintenance of BBB structure, function, or gene expression in the healthy brain. However, we found that PLX5622 treatment alters brain endothelial cholesterol metabolism, and this effect was independent from microglial depletion, suggesting PLX5622 has off-target effects on brain vasculature.
2024-05-22 | GSE267591 | GEO