Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single-cell Sequencing of Microglia following Repopulation Reveals Distinct Clusters and Transcriptomic Signatures in the 3xTg Alzheimer's Disease Model

ABSTRACT: In this study, we aimed to deplete the aging microglia and investigate the impact of the newly-born microglia in Alzheimer's pathology using the 3xTg mouse model. Specifically, >24 mo male 3xTg mice were given chow containing 1200mg/kg PLX5622 (AIN-76A-D1001i, Research Diests, NJ, USA) for 2 weeks to deplete their microglia. Control diet with the same base formula were given to control group and to experimental groups during a 4-week repopulation phase immediately following PLX treatment. At the end of the repopulation, we pooled sorted, viable microglia (CD45int CD11b) from 3-5 mice/group and ran single-cell RNAseq analysis to determine the similarities and differences between the aged and repopulated cells in the context of Alzheimer's Disease. We also included non-transgenic controls as a separate group.

ORGANISM(S): Mus musculus

PROVIDER: GSE190607 | GEO | 2022/02/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Lateral ventricle SVZ: 3xTg vs WT

Project description:Transcriptional profiling of the microdissected SVZ from 7-month-old mice Adult neurogenesis is suppressed in the SVZ of 3xTg mice, a model of Alzheimer's disease. To better understand the underlying mechanisms of this suppression, the goals of this experiment were to compare the transcriptional profiles of the SVZ neural stem cell niche in 3xTg-AD mice versus strain controls. We used early middle-aged mice (7-months-old) rather than old mice, in order to identify genetic changes that are not caused secondarily to other degenerative changes occurring in these mice. Two-condition experiment, 3xTg vs WT SVZ. Biological replicates: 4 for each.

2015-08-01 | E-GEOD-60460 | biostudies-arrayexpress

Lateral ventricle SVZ: 3xTg vs WT

2015-08-01 | GSE60460 | GEO

Gene expression of macrophages isolated from mouse brains

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

Single-cell Sequencing of Microglia following Repopulation Reveals Distinct Clusters and Transcriptomic Signatures in the 3xTg Alzheimer's Disease Model

Project description:Single-cell Sequencing of Microglia following Repopulation Reveals Distinct Clusters and Transcriptomic Signatures in the 3xTg Alzheimer's Disease Model

| PRJNA787636 | ENA

Single cell RNA-sequencing of NK cells from control wildtype and 3XTg-AD mice

Project description:The goal of this study is to examine the single-cell transcriptomes of NK cells from the brains of 3XTg-AD and control wildtype mice. The data generated will elucidate the transcriptomal changes of NK cells in the pro-inflammatory microenvironment of mice with Alzheimer's disease pathologies.

2020-06-08 | GSE142853 | GEO

Bulk RNA-sequencing of microglia in 3XTg-AD mice treated with anti-Nk1.1 depleting antibodies or isotype control

Project description:The goal of this experiment is to determine the effects of NK cells on microglia inflammation in 3XTg-AD mice. We examined the transcriptomal changes of microglia in mice treated with anti-NK1.1 anitbodies and isotype controls by deep RNA-Seq.

2020-06-08 | GSE142875 | GEO

Microglial repopulation reverses cognitive-associated deficits in an Alzheimer’s disease model by restoring the BDNF signaling

Project description:Over the past decade, genetic evidence has demonstrated that microglial dysregulation is likely to play a central role in the development of Alzheimer's disease (AD). As resident immune cells in the brain, microglia become dystrophic and senescent during the chronic progression of AD. To explore whether replenishing the brain with new microglia is beneficial to AD, we employed a CSF1R inhibitor PLX3397 to deplete microglia and induce repopulation after the inhibitor withdrawal in 5xFAD transgenic mice. We observed that microglial repopulation ameliorates AD-associated cognitive deficits, accompanied by elevation of synaptic proteins and hippocampal long-term potentiation (LTP). In addition, microglial morphology is restored after microglial self-renewal, and amyloid pathology is reduced with long-term repopulation but not short-term. Transcriptome analysis showed that repopulating microglia in 5xFAD mice recovers a gene expression profile that is highly similar to microglia from WT mice. Notably, the neurotrophic signaling pathway and hippocampal neurogenesis dysregulated in the AD brain are restored after microglial replenishment. At last, we confirmed that microglial repopulation rescues brain-derived neurotrophic factor (BDNF) expression to contribute to synaptic plasticity. Together, we conclude that microglial self-renewal benefits AD brain by restoring the BDNF neurotrophic signaling pathway. Thus, the proper replenishment of microglia may be an effective and novel therapeutic strategy for ameliorating cognition impairment in AD.

2023-07-24 | GSE223156 | GEO

Microglia are not necessary for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism (Liver Seq)

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

Microglia are not necessary for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism (Brain Endo Bulk Seq)

2024-05-22 | GSE267592 | GEO

Microglia are not necessary for maintenance of blood-brain barrier properties in health, but PLX5622 alters brain endothelial cholesterol metabolism (Brain Endo SC Seq)

2024-05-22 | GSE267591 | GEO