Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Characterization of extracellular micronuclei

ABSTRACT: Microglia, resident immune cells in the central nervous system, undergo morphological and functional changes in response to signals from the local environment and mature into various homeostatic states. However, niche signals underlying microglial differentiation and maturation remain unknown. Here, we show that neuronal micronuclei transfer to microglia, which is followed by changing microglial characteristics during the postnatal period. Neurons passing through a dense region of the developing neocortex give rise to micronuclei and release them into the extracellular space, before being incorporated into microglia and inducing morphological changes. Two-photon imaging analyses have revealed that microglia incorporating micronuclei tend to slowly retract their processes. Loss of the cGAS gene alleviates effects on micronucleus-dependent morphological changes. Neuronal micronuclei-harboring microglia also exhibit unique transcriptome signatures. These results demonstrate that neuronal micronuclei serve as niche signals that transform microglia, and provide a potential mechanism for regulation of microglial characteristics in the early-postnatal neocortex.

INSTRUMENT(S): Q Exactive HF, Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Fuminori Tsuruta

LAB HEAD: Fuminori Tsuruta

PROVIDER: PXD056089 | Pride | 2024-12-29

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	checksum.txt	Txt
	micronuclear_fraction.mgf	Mgf
	micronuclear_fraction.mztab	Mztab
	micronuclear_fraction.raw	Raw

Items per page:

1 - 4 of 4

Similar Datasets

Transcriptome signature of mouse embryonic stem cell-derived microglia is closely related to primary cultured microglia

Project description:Preparation of primary microglial cultures from postnatal mice is tedious with a low yield, high variability and risk of astrocytic contamination. Microglia derived from embryonic stem cells (ESdM) have been suggested as alternative source, but it is unclear how closely ESdM resemble the molecular phenotype of primary microglia. Here, we performed a whole transcriptome analysis of ESdM in comparison to primary cultured and flow cytometry-sorted microglia and compared the microglial transcriptome to other cell types. Cultured microglia and ESdM were related to sorted microglia, but clearly distinct from other myeloid cell types, T cells, astrocytes and neurons. ESdM and primary cultured microglia showed strong overlap in their transcriptome. Only 144 gene transcripts were differentially expressed between both cell types, mainly derived from immune-related genes with a higher activation status of pro-inflammatory and immune defense genes in primary microglia compared to ESdM. Flow cytometry analysis of cell surface markers CD54, CD74 and CD274 selected from the microarray confirmed the close phenotypic relation between ESdM and primary cultured microglia. Thus, assessment of genome-wide transcriptional regulation demonstrates that microglia are distinct from other macrophage cell types and that mouse pluripotent stem cell-derived microglia are closely related to cultured postnatal microglia. Comparison of different primary neuronal cells with ES-cell derived microglial cells

2013-07-11 | E-GEOD-43808 | biostudies-arrayexpress

Pyramidal neuron subtype diversity governs microglia states in the neocortex [MERFISH]

Project description:Microglia are the resident immune cells of the brain, and have critical roles in circuit development and plasticity. During embryonic and postnatal development, microglia exist in multiple transcriptional states. However, it is still poorly understood how these states are established, and whether they are influenced by their cellular environment. Here we show that in the juvenile neocortex, microglia exist in multiple states whose identity and laminar distribution is instructed by the neuronal class identity of local pyramidal neurons. Using single-cell RNA sequencing, we unveil molecular signatures of distinct microglia sub-states, and show that they can be divided into layer-restricted or broadly-distributed states. Strikingly, conversion of deep-layer pyramidal neurons to an alternate class identity reconfigures both the density and molecular state of local layer-restricted microglia to correspond to the new neuronal niche, thus identifying specific populations of microglia that are sensitive to pyramidal neuron subtypes. Ligand-receptor interactomes for individual neuronal subtype-microglia pairings uncovers two categories of neuron-to-microglia communication: one associated with neuronal class identity and one associated with microglial state. Our findings highlight the fundamental role that neuronal identity and neuronal niches play in locally controlling the transcriptional status of postnatal microglia.

2022-04-26 | GSE193760 | GEO

Projection neuron subtypes establish microglia sub-states and regulate neuroimmune interactions

2022-04-26 | GSE158096 | GEO

Microglial SHIP1 controls synaptic pruning in the developing hippocampus via the complement system

Project description:INPP5D, which encodes the lipid phosphatase SHIP1, is one of the most common genes associated with the risk of Alzheimer’s disease and is enriched in microglia in the central nervous system. SHIP1 has been found to be highly expressed in plaque-associated microglia. However, how it regulates microglial function and influences brain physiology has been poorly investigated. Here we show that SHIP1 is not only enriched in microglia associated with amyloid beta plaques, but also in early stages of healthy brain development. By combining in vivo loss-of-function approaches and proteomics, we discovered that conditional knockout mice lacking microglial SHIP1 (cKO) display increased complement and synapse loss in the early postnatal brain. Additionally, SHIP1 KO microglia show reduced morphological complexity, altered transcriptional signatures, and abnormal synaptic pruning, which is dependent on the complement system. Single nucleus RNA-sequencing analysis of the entire hippocampus confirmed decreased interaction for synaptic structure-related pathways in both excitatory and inhibitory neurons. Importantly, cKO mice show cognitive defects in adulthood only when microglial SHIP1 is depleted at early postnatal days, but not when depleted at later stages. Finally, using CRISPR/Cas9 we generated human iPSC-derived microglia lacking SHIP1, and validated the increased engulfment of synaptic structures. Altogether, these findings suggest that SHIP1 is essential for proper microglia-mediated synapse remodeling through the complement system in the early postnatal brain. Disrupting this process has lasting behavioral effects and may provide a link to vulnerability to neurodegeneration.

2024-12-04 | PXD052118 | Pride

Mus musculus

Project description:Regulation of microglial states by neuronal micronuclei

| PRJDB15502 | ENA

Polarized microtubule remodeling transforms activated microglia morphology and drives cytokine release

Project description:Microglial activation is a pathological hallmark in many neurodegenerative diseases. During activation, microglia undergo complex morphological changes, including loss of their characteristic ramified cell morphology, which is routinely used to detect and quantify inflammation in the brain. However, the molecular mechanisms enabling this morphological change and the relation between microglial cell morphology and its pathophysiological function are not understood. Here, proteomic profiling of activated microglia identified microtubule remodeling pathways as an early factor that drives the morphological change and subsequently controls cytokine responses. We found that activated microglia increase their microtubule dynamics to form a stable and centrosomally anchored microtubule array to facilitate efficient cytokine trafficking and release. Moreover, we identified cyclin-dependent kinase 1 (Cdk-1) as a critical upstream regulator of microtubule remodeling and morphological change in vitro and in vivo. These results demonstrate a critical role for microtubule dynamics and reorganization in microglial activation and modulating cytokine-mediated inflammatory responses.

| MSV000090254 | MassIVE

Sorted cells_PS2APP brains_7/13mo

Project description:Mice of indicated ages and genotypes were perfused and their brains dissected and dissociated. Cells were fixed, immunolabeled and FACS sorted. RNA was extracted from neuron, astrocyte, and microglial cell populations. Typical RIN=4-5 for neurons, 6-8 for astrocytes, and 5-7 for microglia. Typical RNA yields ~100ng for neurons, ~20ng for microglia, and ~10ng for astrocytes. cDNA was generated from up to 25 ng of total RNA using Nugen's RNA-Seq method for low-input RNA samples, Ovation RNA-Seq System V2 (NuGEN). (Per manufacturers instructions, total RNA was neither depleted of rRNA nor polyA-selected.) 1 ug of sheared cDNA was taken into further processing, starting at end repair step, using Illumina's TruSeq RNA Sample Preparation Kit v2 (Illumina). The 'SAMPLE_ID'; sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech's ExpressionPlot database is PRJ0006149 Astrocytes, microglia and neurons were sorted from 7- or 13-month old PS2APP or non-transgenic mice, 4 <= n <= 7 per group.

2016-01-26 | E-GEOD-75431 | biostudies-arrayexpress

Microglial response to A? and prostaglandin-E2 EP4 receptor activation

Project description:A persistent and non-resolving inflammatory response to accumulating A? peptide species is a cardinal feature in the development of Alzheimer's disease (AD). In response to accumulating A? peptide species, microglia, the innate immune cells of the brain, generate a toxic inflammatory response that accelerates synaptic and neuronal injury. Many pro-inflammatory signaling pathways are linked to progression of neurodegeneration. However, endogenous anti-inflammatory pathways capable of suppressing A?-induced inflammation represent a relatively unexplored area. Here we hypothesized that signaling through the prostaglandin-E2 (PGE2) EP4 receptor potently suppresses microglial inflammatory responses to A?42 peptides. In cultured microglial cells, EP4 stimulation attenuated levels of A?42-induced inflammatory factors and potentiated phagocytosis of A?42. Microarray analysis was performed and demonstrated that EP4 stimulation broadly opposed A?42-driven gene expression changes in microglia, with enrichment for targets of IRF1, IRF7, and NF-?B transcription factors. Primary microglia were isolated from the brains of postnatal day 7 C57BL/6J mouse pups using the Neural Tissue Dissociation Kit (P), MACS Separation Columns (LS), and magnetic CD11b Microbeads from Miltenyi Biotec (Auburn, CA). Microglia from three separate litters of pups were maintained as three independent biological replicates for each treatment. After being cultured for three days, microglia were treated with oligomeric A?42 (10uM) and/or the specific EP4 agonist AE1-329 (100nM) for 6 hours. These 4 treatment conditions (A? + AE1, A? alone, AE1 alone, and vehicle alone) and 3 independent biological replicates per treatment gave us 12 total samples. After 6 hours of treatment, RNA was isolated from the microglia for microarray analysis.

2014-04-25 | E-GEOD-55627 | biostudies-arrayexpress

Microglial SHIP1 controls synaptic pruning in the developing hippocampus via the complement system

2024-12-09 | GSE279176 | GEO

Polygenic Risk for Alcohol Use Disorder Affects Cellular Responses to Ethanol Exposure in a Human Microglial Cell Model I

Project description:Polygenic risk scores (PRS) assess genetic susceptibility to Alcohol Use Disorder (AUD), yet their molecular implications remain underexplored. Neuroimmune interactions, particularly in microglia, are recognized as significant contributors to AUD pathophysiology. We investigated the interplay between AUD PRS and ethanol in human microglia derived from iPSCs from individuals with high-or low-PRS (HPRS or LPRS) of AUD. Ethanol exposure induced elevated CD68 expression and morphological changes in microglia, with differential responses between HPRS and LPRS microglial cells. Transcriptomic analysis revealed expression differences in MHCII complex and phagocytosis-related genes following ethanol exposure; HPRS microglial cells displayed enhanced phagocytosis and increased CLEC7Aexpression, unlike LPRS microglial cells. Synapse numbers in co-cultures of induced neurons with microglia after alcohol exposure were lower in HRPS co-cultures, suggesting possible excess synapse pruning. This study provides insights into the intricate relationship between AUD PRS, ethanol, and microglial function, potentially influencing neuronal functions in developing AUD.

2024-02-19 | GSE255988 | 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