Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Interaction between subventricular zone microglia and neural stem cells impacts the neurogenic response in a mouse model of cortical ischemic stroke

ABSTRACT: After a stroke, the neurogenic response from the subventricular zone (SVZ) to repair the brain is limited. Microglia, as an integral part of the distinctive SVZ microenvironment, control neural stem / precursor cell (NSPC) behavior. Here, we show that discrete stroke-associated SVZ microglial clusters negatively impact the innate neurogenic response, and we propose a repository of relevant microglia–NSPC ligand–receptor pairs. After photothrombosis, a mouse model of ischemic stroke, the altered SVZ niche environment leads to immediate activation of microglia in the niche and an abnormal neurogenic response, with cell-cycle arrest of neural stem cells and neuroblast cell death. Pharmacological restoration of the niche environment increases the SVZ-derived neurogenic repair and microglial depletion increases the formation and survival of newborn neuroblasts in the SVZ. Therefore, we propose that altered cross-communication between microglial subclusters and NSPCs regulates the extent of the innate neurogenic repair response in the SVZ after stroke.

ORGANISM(S): Mus musculus

PROVIDER: GSE275939 | GEO | 2024/09/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Jedi-1/MEGF12-mediated phagocytosis controls the pro-neurogenic properties of microglia in the ventricular-subventricular zone

Project description:Microglia are the primary phagocytes in the central nervous system and are responsible for clearing dead cells generated during development or disease. The phagocytic process shapes the phenotype of the microglia, which affects the local environment. A unique population of microglia reside in the ventricular-subventricular zone (V-SVZ) of neonatal mice, but how they influence this neurogenic niche is not well-understood. Here, we demonstrate that phagocytosis creates a pro-neurogenic microglial phenotype in the V-SVZ and that these microglia phagocytose apoptotic cells via the engulfment receptor Jedi-1. Deletion of Jedi-1 decreases apoptotic cell clearance, triggering the development of a neuroinflammatory phenotype, reminiscent of neurodegenerative and-age-associated microglia, that reduces neural precursor proliferation via elevated interleukin (IL)-1β signaling; inhibiton of IL-1 receptor rescues precursor proliferation in vivo. Together, these results reveal a critical role for Jedi-1 in connecting microglial phagocytic activity to a phenotype that promotes neurogenesis in the developing V-SVZ. We performed RNAseq on MACS-sorted microglia from V-SVZ and Cortex of WT and Jedi-1 knockout P7 mice.

2024-02-15 | GSE232441 | GEO

Transcriptional profiling by RNA-seq in Dbx2-overexpressing cultures of adult neural progenitors

Project description:In selected tissutal niches of the adult mouse brain, such as the subventricular zone (SVZ) underlying the lateral ventricles, neurogenesis persists thanks to a population of quiescent neural stem cells, which can be activated (aNSCs) by extrinsic stimuli to initiate proliferation and generate a neurogenic lineage consisting of transit amplifying progenitors (TAPs), neuroblasts (NBs) and newborn neurons. This process is markedly reduced during aging, which might contribute to the cognitive decline of elderly subjects. Recent studies suggest that the aged niche environment may decrease the pool of proliferating neural/stem progenitor cells (NSPCs), and hence adult neurogenesis, by causing transcriptomic changes that favour NSC quiescence over activation. The transcription factors that mediate these changes, however, remain largely unclear. We previously found that the homeobox gene Dbx2 is upregulated in NSPCs of the aged mouse SVZ and can inhibit the growth of young adult NSPC cultures. Here, we show that Dbx2 expression is downregulated by Epidermal Growth Factor Receptor signalling, which promotes NSPC proliferation and decreases in the aged SVZ. By means of transgenic NSPC lines, we also show that Dbx2 inhibits NSPC proliferation by hindering the G1/S and the G2/M transition. Furthermore, we exploit RNA sequencing of transgenic NSPCs to elucidate the transcriptional networks modulated by Dbx2. Among the top hits, we report the downregulation of several gene categories implicated in cell cycle progression. Accordingly, we find that Dbx2 function is negatively correlated with the transcriptional signatures of proliferative NSPCs (aNSCs, TAPs and early NBs). Altogether, these results point to Dbx2 as a potential molecular node relaying the extracellular anti-neurogenic input of the aged niche to the NSPC transcriptome.

2023-11-29 | GSE222691 | GEO

Single cell approached deine forebrain neural stem cell niches and identify microglial ligands that enhance precursor-mediated remyelination (Xenium)

Project description:Here we used single cell RNA-sequencing and single cell spatial transcriptomics to characterize the forebrain neural stem cell (NSC) niche under homeostatic and injury conditions. We define the dorsal and lateral ventricular-subventricular zones (V-SVZ) as two distinct neighborhoods, and show that following white matter injury, dorsal NSCs are locally activated to make oligodendrocytes for remyelination. This activation is coincident with a robust increase in transcriptionally-distinct microglia in the dorsal V-SVZ niche. We modeled ligand-receptor interactions within this changing niche and identified two remyelination-associated microglial ligands, IGF1 and OSM, that promote precursor proliferation and oligodendrogenesis in culture. Infusion of either ligand into the lateral ventricles also enhanced oligodendrogenesis, even in the lateral V-SVZ, where NSCs normally make neuroblasts. These data support a model where gliogenesis versus neurogenesis is determined by the local NSC neighborhood and where injury-induced niche alterations promote NSC activation, local oligodendrogenesis, and likely contribute to myelin repair.

2024-12-20 | GSE266689 | GEO

Single cell approaches define forebrain neural stem cell niches and identify microglial ligands that enhance precursor-mediated remyelination (MERFISH)

2024-12-20 | GSE266688 | GEO

Single cell approaches define forebrain neural stem cell niches and identify microglial ligands that enhance precursor-mediated remyelination (scRNA-Seq)

2024-12-20 | GSE266687 | GEO

Microglia in ischemic brain injury

Project description:Microglia are resident CNS immune cells that are active sensors in healthy brain and versatile effectors under pathological conditions. Cerebral ischemia induces a robust neuroinflammatory response that includes marked changes in the gene expression and phenotypic profile of a variety of endogenous CNS cell types (astrocytes, neurons, microglia) as well as an influx of leukocytic cells (neutrophils, macrophages, T-cells) from the periphery. Many molecules and conditions can trigger a transformation of ârestingâ (or surveying) microglia to an âactivatedâ (alerted/reactive) state. Here we review recent developments in the literature that relate to microglial activation in the experimental setting of in vitro and in vivo ischemia. We also present new data from our own laboratory demonstrating the direct effects of in vitro ischemic conditions on the microglial phenotype and genomic profile. Emphasis is placed on the role of specific molecular signaling systems such as hypoxia inducible factor-1 (HIF-1) and toll-like receptor-4 (TLR4) in regulating the microglial response in this setting. We then review histological and recent novel radiological data that confirms a key role for microglial activation in the setting of ischemic stroke in humans. We discuss recent progress in the pharmacological and molecular targeting of microglia in acute ischemic stroke. Finally, we explore how recent studies on ischemic preconditioning have increased interest in preemptively targeting microglial activation in order to reduce stroke severity. 12 arrays, 4 experimental groups, 3 replicates in each group, CN is control normoxia, CH is control hypoxia, TN is TLR4 knockout normoxia, TH is TLR4 knockout hypoxia.

2010-10-05 | E-GEOD-18602 | biostudies-arrayexpress

Defining the microglial transcriptome in the rat subventricular zone (SVZ) after neonatal hypoxia-ischemia (HI).

Project description:Purpose: Recent findings indicate a regulatory role of microglia on neurogenesis in the SVZ in health and disease. Microglia in the early postnatal SVZ are not fully maturated and may react differently than adult microglia to injury. We sought to investigate the impact of cortico-striatal neonatal HI injury on the microglial phenotype in the early postnatal SVZ. Results: In comparison to sham SVZ microglia, HI SVZ microglia upregulate both pro- and anti-inflammatory genes as well as neurotrophic genes. HI SVZ microglia do not adopt a M1 or M2 polarization state, but instead share commonly expressed genes with microglia in rodent models of neurodegenerative diseases.

2020-01-13 | GSE97299 | GEO

Microglia transcriptome in a rat model of ischemic stroke

Project description:Microglia are key regulators of inflammatory response after stroke and brain injury. Here we profiled the microglia transcriptome isolated from a spontaneously hypertensive rat model of focal cerebral ischemia. We identified an extensive and persistent upregulation of anti-inflammatory M2-like patterns after stroke and a mild up-regulation of pro-inflammatory M1-like patterns at later stage. We also found that younger brains showed larger microglial response than middle aged brains. Moreover, beyond the standard M1/M2 dichotomy, a wide spectrum of novel microglial polarization states was activated in response to stroke, particularly the phenotypes related to Tlr2 and dietary fatty acids stimulation.

2020-04-24 | GSE148350 | GEO

Differential Expression Data from Mice 24hrs after stroke

Project description:Microglial activation after stroke may lead to development of inflammation-induced brain damage. Here we uncover a ribosome-based mechanism/check point involved in control of the innate immune response and microglial activation orchestrated by RNA binding protein SRSF3. Using an in vivo model-system for analysis of the dynamic translational state of microglial ribosomes with mRNAs as input and newly synthesized peptides as an output, we found a marked dissociation of microglia mRNA and protein signatures following ischemic stroke. Highly up-regulated and ribosomes associated mRNAs were not translated 24hrs after stroke resulting in two distinct microglial molecular signatures, a highly specialized pro-inflammatory mRNA and immunomodulatory/homeostatic protein signatures. We found that this is due to specific translational suppression of highly expressed mRNAs through a 3'UTR-mediated mechanism involving the RNA binding protein SRSF3. This discovery suggests avenues for therapeutic modulation of innate immune response in resident microglia after stroke.

2024-04-30 | GSE232244 | GEO

H3K9me3 ChIP-Seq of baboon SVZ primary cells

Project description:Histone 3 Lysine 9 (H3K9) methylation is known to be associated with pericentric heterochromatin and important in genomic stability. In this study, we show that trimethylation at H3K9 (H3K9me3) is enriched in an adult neural stem cell niche- the subventricular zone (SVZ) on the walls of the lateral ventricle in both rodent and non-human primate baboon brain. Previous studies have shown that there is significant correlation between baboon and human regarding genomic similarity and brain structure, suggesting that findings in baboon are relevant to human. To understand the function of H3K9me3 in this adult neurogenic niche, we performed genome-wide analyses using ChIP-Seq (chromatin immunoprecipitation and deep-sequencing) and RNA-Seq for in vivo SVZ cells purified from baboon brain. Through integrated analyses of ChIP-Seq and RNA-Seq, we found that H3K9me3-enriched genes associated with cellular maintenance, post-transcriptional and translational modifications, signaling pathways, and DNA replication are expressed, while genes involved in axon/neuron, hepatic stellate cell, or immune-response activation are not expressed. As neurogenesis progresses in the adult SVZ, cell fate restriction is essential to direct proper lineage commitment. Our findings highlight that H3K9me3 repression in undifferentiated SVZ cells is engaged in the maintenance of cell type integrity, implicating a role for H3K9me3 as an epigenetic mechanism to control cell fate transition within this adult germinal niche. SVZ H3K9me3 ChIP-seq profile of an adult baboon subventricular zone was generated by deep sequencing with Illumina HiSeq2000

2014-10-01 | E-GEOD-59074 | biostudies-arrayexpress

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