Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Astrogenesis in the murine dentate gyrus – a life-long and plastic process mediated by proliferation of neural stem cells and local astrocytes

ABSTRACT: Astrocytes are highly abundant cells in the mammalian brain and their numerous functions are of vital importance for all aspects of development, adaption and aging of the central nervous system (CNS). Mounting evidence indicates the astrocytes’s cardinal contribution to a wide range of neuropathies, still, our understanding of astrocyte development significantly lags behind those of other CNS cells. Using the dentate gyrus (DG) as a model system, we here combine genetic fate-mapping, behavioral paradigms, single cell transcriptomics and in vivo two-photon imaging, to assess the generation and proliferation of astrocytes across the lifespan of a mouse in great detail. Astrogenesis in the DG is initiated by perinatal radial glia-like neural stem cells (rNSCs) giving rise to locally dividing astrocytes that enlarge the astrocyte compartment in an outside-in-pattern. This process occurs simultaneously to neurogenesis and likewise continues life-long. In the adult DG, rNSCs occasionally give rise to newborn astrocytes, but the vast majority of astrogenesis is mediated through proliferation of local astrocytes. Interestingly, locally dividing astrocytes revealed an unexpected plasticity and were able to adapt their proliferation to environmental and behavioural stimuli. Our study thus establishes astrocytes as enduring plastic elements in DG circuits, implicating a vital contribution of astrocyte dynamic to hippocampal plasticity.

ORGANISM(S): Mus musculus

PROVIDER: GSE190399 | GEO | 2021/12/12

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

Effects of Pd1 targeted myeloid deletion on brain development

Project description:During early brain development, the nervous system continues to evolve and improve, and cells in different stages contact and connect to form a unique nervous system network. Various cross-talk between cell populations is the key to neurological homeostasis. Communication between astrocytes and myeloid cells affects brain function. Programmed cell death protein 1 (PDCD1), also known as PD-1 or CD279 (differentiation cluster 279), is a member of the immunoglobulin gene superfamily. Here, we investigated the loss of PD-1 in myeloid cells results in abnormal development of the nervous system. Specific ablation of PD-1 affects myeloid cell proliferation and subtype classification. At the stage of astrogenesis onset, the astrocyte proliferation ends, and the continuous development, the results of immunofluorescence staining with different astrocyte markers show that astrocytes-related genes were highly expressed in PD-1f/flysMCre mice. PD-1f/flysMCre mice exhibited more outgoing, less anxious, and a more extroverted mode of exploration in behavioral tests. The specific ablation of PD-1 increases the expression of CXCL1 through the NF-κB signaling pathway. It reaches the brain and interacts with CXCR2 on astrocytes, promoting astrocyte proliferation. Our results not only reveal an important regulatory role of PD-1 in myeloid cells on astrocytes but also provide some theoretical basis and ideas for the study of myeloid and brain axis

2024-09-30 | GSE277873 | GEO

RNA-Seq of human astrocytes

Project description:Astrocytes were purified from fetal and adult human brain tissue using an immunopanning method with the HepaCAM antibody. Samples were taken from otherwise 'healthy' pieces of tissue, unless otherwise specified. 6 fetal astrocyte samples, 12 adult astrocyte samples, 8 GBM or sclerotic hippocampal samples, 4 whole human cortex samples, 4 adult mouse astrocyte samples, and 11 human samples of other purified CNS cell types

2015-12-11 | E-GEOD-73721 | biostudies-arrayexpress

Astrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1

Project description:Astrocytic morphogenesis and maturation are critical steps in CNS development. The time window of astrocyte morphological development is well defined, but the molecular underpinnings are still unclear. BDNF is a critical growth factor involved in the development of the CNS, including synapse refinement. Here we demonstrate the BDNF receptor at Ntrk2 is enriched in astrocytes relative to all CNS cell populations. RNA sequencing indicates Ntrk2 falls in the top 0.001% of all gene transcripts expressed in juvenile astrocytes, almost exclusively due to truncated TrkB.T1. Astrocyte complexity is increased in the presence of BNDF in vitro, which is dependent upon the presence of TrkB.T1. Furthermore, deletion of TrkB.T1 in vivo revealed astrocytes with significantly reduced volume and branching complexities. Indicating a role for functional astrocyte maturation via BDNF/TrkB.T1 signaling, TrkB.T1 KO astrocytes do not support normal excitatory synaptogenesis. Together, these data suggest a significant role for BDNF/TrkB.T1 signaling in astrocyte morphogenesis and indicate this signaling may contribute to astrocyte regulation of neuronal synapse development.

2019-08-26 | GSE122176 | GEO

A Molecular Switch for Neuroprotective Astrocyte Reactivity

Project description:Astrocytes differentiate into a spectrum of neurotoxic and neuroprotective reactive subpopulations after CNS injury and in disease. In astrocyte conditional ADCY10 (sAC) knockout mice, reactive astrocytes exhibit a shift towards neurotoxic phenotypes implicating sAC as a critical regulator of neuroprotective astrocyte differentiation.

2023-12-11 | GSE237675 | GEO

Transcriptomic response of human primary astrocytes to two different variants of SARS-CoV-2

Project description:A pivotal role of astrocytes in the pathophysiology of CNS disorders during the SARS-CoV-2 infection of brain has been proposed. Thus, the study was performed to reveal astrocyte response to infection caused by either Omicron or Delta variant.

2025-03-01 | E-MTAB-14745 | biostudies-arrayexpress

Mouse primary astrocytes: LCN2 protein treated vs. control

Project description:Transcriptional profiling of mouse primary astrocytes comparing control untreated astrocytes with astrocytes treated with recombinant LCN2 protein (10 micro gram/ml). Goal was to determine the effects of LCN2 treatment on global gene expression in astrocytes. A secreted protein lipocalin-2 (LCN2) has been implicated in diverse cellular processes including cell morphology and migration. We have previously demonstrated that lcn2 mediates reactive astrocytosis. In order to further understand the role of lcn2 in the CNS, astrocyte transcriptome was analyzed following LCN2 treatment. Chemokines were the major group of genes upregulated by LCN2. Two-condition experiment, control untreated astrocytes vs. LCN2 protein treated astrocytes. Biological replicates: 1 control replicates, 1 treated replicates.

2012-06-29 | E-GEOD-15667 | biostudies-arrayexpress

Astrocyte and neuron subcompartment proteomes reveal distinct cellular and molecular mechanisms of OCD

Project description:Astrocytes and neurons coexist and interact in the CNS1,2. Given that many signaling and pathological events are protein-driven, identifying astrocyte and neuron proteomes is essential for elucidating the complex protein networks that dictate their respective contributions to physiology and disease. Here, we used cell- and subcompartment-specific proximity-dependent biotinylation3 to study the proteomes of striatal astrocytes and medium spiny neurons (MSNs) in vivo. We evaluated cytosolic and plasma membrane compartments for astrocytes and MSNs, revealing how these cells differ at the protein level and in their core signaling machinery. We assessed subcellular compartments of astrocytes including end feet and processes to reveal the molecular basis of essential astrocyte signaling and homeostatic functions. Unexpectedly, SAPAP3 proteins (gene; Dlgap3) associated with obsessive compulsive disorder (OCD) and repetitive behaviors4-11 were detected at equivalent levels in striatal astrocyte and MSN plasma membrane and cytosolic compartments. Astrocytic expression was confirmed by RNA-seq, fluorescence in situ hybridization and immunohistochemistry. Furthermore, genetic rescue experiments combined with behavioral analyses and proteomics in a mouse model4 of OCD lacking SAPAP3 revealed contributions of SAPAP3 in astrocytes and MSNs to repetitive and anxiety-related OCD behaviors. Our data define how astrocytes and neurons differ at the protein level and in their major signaling pathways, how astrocyte proteomes vary between physiological subcompartments, and how specific astrocyte and neuronal molecular mechanisms contribute to a psychiatric disease. Targeting both astrocytes and neurons together is likely to be therapeutically effective in complex CNS disorders.

2023-01-13 | PXD029257 | Pride

Insights into responses of human astrocytes to H5N1 infection by transcriptional analysis

Project description:Increasing evidence demonstrates influenza virus can not only affect the respiratory system, but also infect CNS and lead to CNS disorder and encephalopathy and encephalitis. Astrocytes are the most abundant cells in the CNS, which are capable of producing cytokines and neurotrophic factors and are essential for brain homeostasis and neuronal function. Previous studies suggested that influenza virus can infect astrocytes and induce proinflammatory cytokines response as well as apoptosis. Nevertheless, very few mechanistic data are available regarding host responses to H5N1 infection in astrocytes. In this study, a functional genomics approach was utilized to investigate comprehensive host responses to H5N1 infection in a human astrocyte cell line, U251 cells. U251 cells were infected by H5N1 at MOI 1 or control . At time points 6, 12, and 24h, total RNA were extracted for microarray experiment. Three replicates were performed at each time point of infection and control infection.

2016-01-04 | E-GEOD-66597 | biostudies-arrayexpress

A Molecular Switch for Neuroprotective Astrocyte Reactivity

Project description:The intrinsic mechanisms that regulate neurotoxic versus neuroprotective astrocyte phenotypes and their effects on central nervous system (CNS) degeneration and repair remain poorly understood. Here, we show injured white matter astrocytes differentiate into two distinct C3-positive and C3-negative reactive populations, previously simplified as neurotoxic (A1) and neuroprotective (A2)1,2, which can be further subdivided into unique subpopulations defined by proliferation and differential gene expression signatures. We find the balance of neurotoxic versus neuroprotective astrocytes is regulated by discrete pools of compartmented cAMP derived from soluble adenylyl cyclase (sAC) and show proliferating neuroprotective astrocytes inhibit microglial activation and downstream neurotoxic astrocyte differentiation to promote retinal ganglion cell (RGC) survival. Finally, we report a new, therapeutically tractable viral vector to specifically target optic nerve head astrocytes and show elevating nuclear or depleting cytoplasmic cAMP in reactive astrocytes inhibits deleterious immune cell infiltration and promotes RGC survival after optic nerve injury. Thus, soluble adenylyl cyclase and compartmented, nuclear- and cytoplasmic-localized cAMP in reactive astrocytes act as a molecular switch for neuroprotective astrocyte reactivity that can be targeted to inhibit microglial activation and neurotoxic astrocyte differentiation to therapeutic effect. These data expand upon and define new reactive astrocyte subtypes and represents a novel step towards the development of gliotherapeutics for the treatment of glaucoma and other optic neuropathies.

2023-12-11 | GSE245816 | GEO

Expression data from reactive astrocytes acutely purified from young adult mouse brains

Project description:Reactive astrogliosis is characterized by a profound change in astrocyte phenotype in response to all CNS injuries and diseases. To better understand the reactive astrocyte state, we used Affymetrix GeneChip arrays to profile gene expression in populations of reactive astrocytes isolated at various time points after induction using two different mouse injury models, ischemic stroke and neuroinflammation. Young adult male mice underwent middle cerebral artery occlusion (MCAO) to produce ischemic stroke or control sham surgery. Young adult mice were injected intraperitoneally with 5 mg/kg lipopolysaccharide (LPS) to produce neuroinflammation or saline for control. Astrocytes were acutely purified from control and injured brains at 1 day after injury for LPS/saline injection and 1, 3 days and 7 days after MCAO/sham surgeries.

2012-05-01 | E-GEOD-35338 | 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