Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A distinct astrocyte subtype in the aging mouse brain characterized by impaired protein homeostasis

ABSTRACT: A distinct astrocyte subtype in the aging mouse brain characterized by impaired protein homeostasis

PROVIDER: PRJNA758929 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR15669469.fastq.gz	Fastqsanger.gz
	SRR15669470.fastq.gz	Fastqsanger.gz
	SRR15669471.fastq.gz	Fastqsanger.gz

Items per page:

1 - 3 of 3

Similar Datasets

A distinct astrocyte subtype in the aging mouse brain characterized by impaired protein homeostasis

Project description:A new population of dysfunctional astrocytes in the aging mouse hippocampus called autophagy-dysregulated astrocytes (APDAs) show impaired protein homeostasis and defective regulation of synapse formation and elimination and appear early in a mouse model of Alzheimer’s disease.

2022-07-19 | GSE183042 | GEO

Astrocyte-enriched pan-brain aging transcriptome

Project description:Normal brain aging is marked by a cognitive decline, spurred by changes in cellular metabolism and homeostatic dysregulation, as well as modifications in synapses and neuronal connectivity. Astrocytes are well positioned as an effector of these changes, although how properties of astrocytes change with age remains unclear. Here, we address this question by profiling astrocytic gene expression from multiple brain regions of adult (4 month-old) and aged (2 years-old) mice. We isolated mRNA from transgenic mice where ribosomes within astrocytes were genetically tagged (GFAP-cre x RPL22-HA, astrocyte ribotag). We then used RNA sequencing to identify and quantify the astrocyte-enriched mRNA, analyzing 4 different brain regions: visual cortex, somatomotor cortex, hypothalamus, and cerebellum. Overall, we find that astrocyte expression of inflammatory and immune response factors increase with age, as well as changes in genes associated with metabolism, cholesterol synthesis, and synaptogenesis. Going forward, these data contribute to an understanding of astrocyte diversity and provide insight into the role of astrocytes in normal aging.

2017-12-11 | GSE99791 | GEO

Spatiotemporal transcriptomic mapping reveals region-specific glial activation and astrocyte subtype shifts in epileptogenesis beyond the hippocampus

Project description:Temporal lobe epilepsy (TLE) is a prevalent neurological disorder often initiated by status epilepticus (SE), followed by a latent phase that culminates in chronic epilepsy. The molecular and cellular mechanisms driving this transformation remain incompletely understood. Here, we applied Visium-based spatial transcriptomics to coronal brain sections from lithium-pilocarpine–induced SE rats and controls (n = 16) to map transcriptional dynamics across epileptogenesis. Spatial clustering accurately defined anatomically relevant regions and canonical markers in controls. Comparative analyses revealed extensive SE-associated transcriptional alterations spanning latent and chronic phases across all examined regions. Notably, spatial profiling demonstrated that microglial activation and reactive astrogliosis extended well beyond the hippocampus, encompassing white matter tracts and multiple thalamic nuclei during the latent phase. Cell-type deconvolution further identified pronounced regional shifts in astrocyte functional subtypes within these reactive zones. These findings uncover the spatial heterogeneity of epileptogenic processes, highlighting previously underappreciated thalamic and white matter involvement. The identification of region-specific glial responses and astrocyte subtype transitions provides new mechanistic insights into epileptogenesis and underscores the need for region- and cell-type–targeted strategies to inform therapeutic interventions in TLE.

2026-02-18 | GSE301260 | GEO

scRNA-seq of electrophysiologically characterized DRG neurons reveals subtype-specific and maturational differences in gene expression

Project description:scRNA-seq of electrophysiologically characterized DRG neurons reveals subtype-specific and maturational differences in gene expression

| PRJNA645297 | ENA

Mutations in CHMP2B Causes Impaired Autophagy and Distorted Energy Metabolism cumulating in Reactive Astrocyte Phenotypes

Project description:Mutations in CHMP2B Causes Impaired Autophagy and Distorted Energy Metabolism cumulating in Reactive Astrocyte Phenotypes

| PRJNA593246 | ENA

Astrocyte-targeting therapy rescues cognitive impairment caused by neuroinflammation via the Nrf2 pathway (ChIP-Seq)

Project description:Neuroinflammation is a common feature of neurodegenerative disorders such as Alzheimer's disease (AD). Neuroinflammation is induced by dysregulated glial activation, and astrocytes, the most abundant glial cells, become reactive upon neuroinflammatory cytokines released from microglia, and actively contribute to neuronal loss. Therefore, blocking reactive astrocyte functions is a viable strategy to manage neurodegenerative disorders. However, factors or therapeutics directly regulating astrocyte subtype remain unexplored. Here, we identified transcription factor NF-E2-related factor 2 (Nrf2) as a therapeutic target in neurotoxic reactive astrocytes upon neuroinflammation. We found that the absence of Nrf2 promoted the activation of reactive astrocytes in the brain tissue samples obtained from AD model 5xFAD mice, whereas enhanced Nrf2 expression blocked the induction of reactive astrocyte gene expression by counteracting NF-kB subunit p65 recruitment. Neuroinflammatory astrocytes robustly upregulated genes associated with type I interferon and the antigen-presenting pathway, which were suppressed by Nrf2 pathway activation. Moreover, impaired cognitive behaviors observed in AD mice were rescued upon ALGERNON2 treatment, which potentiated Nrf2 pathway and reduced the induction of neurotoxic reactive astrocytes. Thus, we highlight the potential of astrocyte-targeting therapy by promoting the Nrf2 pathway signaling for neuroinflammation-triggered neurodegeneration.

2023-08-07 | GSE237423 | GEO

Astrocyte-targeting therapy rescues cognitive impairment caused by neuroinflammation via the Nrf2 pathway ( nascent RNA-Seq )

2023-08-07 | GSE237422 | GEO

Astrocyte-Derived Clusterin Disrupts Glial Physiology to Obstruct Remyelination in Mouse Models of Demyelinating Diseases

Project description:Multiple sclerosis (MS) is a debilitating demyelinating disease characterized by remyelination failure attributed to inadequate oligodendrocyte precursor cells (OPCs) differentiation and aberrant astrogliosis. A comprehensive cell atlas reanalysis of clinical specimens brings to light heightened clusterin (CLU) expression in a specific astrocyte subtype links to active lesions in MS patients. Our investigation reveals elevated astrocytic CLU levels in both active lesions of patient tissues and female murine MS models. CLU administration stimulates primary astrocyte proliferation while concurrently impedes astrocyte-mediated clearance of myelin debris. Intriguingly, CLU overload directly impedes OPCs differentiation and induces OPCs and OLs apoptosis. Mechanistically, CLU suppresses PI3K-AKT signaling in primary OPCs via very low-density lipoprotein receptor. Pharmacological activation of AKT rescues the damage inflicted by excess CLU on OPCs and ameliorates demyelination in the corpus callosum. Furthermore, conditional knockout of CLU emerges as a promising intervention, showcasing improved remyelination processes and reduced severity in murine MS models.

2024-08-23 | GSE275514 | GEO

High inflammatory activity in patients with multiple sclerosis induces a specific astrocyte reactive state that drives non-cell-autonomous neuronal degenerationHigh inflammatory activity in patients with multiple sclerosis induces a specific astrocyte reactive state that drives non-cell-autonomous neuronal degeneration

Project description:Astrocytes contribute to the pathogenesis of multiple sclerosis (MS); however, the mechanisms underlying the regulation of astrocytic responses remain unknown. Here we report an exhaustive molecular and functional characterization of astrocyte reactivity following exposure to cerebrospinal fluid (CSF) from MS patients classified according to the degree of inflammatory activity. We showed that mouse astrocytes exposed to CSF from patients with high inflammatory activity (MS-High) exhibited a specific pro-inflammatory reactive state that was characterized by enhanced NF-kB signalling. This reactive astrocyte state conferred a dysfunctional response through an altered pro-inflammatory secretome that drove neuronal dysfunction and impaired synaptic plasticity. SerpinE1 was identified as a potential downstream mediator of the non-cell-autonomous toxic effect on neuronal function based on its significant up-regulation in secretomes from astrocytes exposed to CSF from MS-high patients. Further, we identified chitinase 3-like 1 as a potential upstream modulator of astrocyte reactivity via activation of NF-kB signalling based on its significantly increased levels in the CSF from MS-High patients. Taken together our findings indicate that the inflammatory microenvironment in the central nervous system of MS patients can induce specific reactive astrocyte states that trigger neuronal degeneration and may ultimately contribute to disease progression.

2022-06-23 | PXD027152 | Pride

H1N1 subtype

Project description:H1N1 subtype

| PRJNA477707 | ENA