Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Infection-induced vascular inflammation in COVID-19 links focal microglial dysfunction with neuropathologies through IL-1/IL-6-related systemic inflammatory states

ABSTRACT: Infection-induced vascular inflammation in COVID-19 links focal microglial dysfunction with neuropathologies through IL-1/IL-6-related systemic inflammatory states

PROVIDER: PRJNA982814 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR24900244_1.fastq.gz	Fastqsanger.gz
	SRR24900244_2.fastq.gz	Fastqsanger.gz
	SRR24900245_1.fastq.gz	Fastqsanger.gz
	SRR24900245_2.fastq.gz	Fastqsanger.gz
	SRR24900246_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 10

Similar Datasets

Infection-induced vascular inflammation in COVID-19 links focal microglial dysfunction with neuropathologies through IL-1/IL-6-related systemic inflammatory states

Project description:COVID-19 is associated with diverse neurological- and inflammatory states that predict poor acute- and long-term outcomes in patients. However, the mechanisms whereby infection-induced inflammation could affect complex neuropathologies through microglia, the main immune cells of the brain, is unclear. We developed a unique autopsy platform allowing the integration of molecular anatomy-, protein- and mRNA data sets in post-mortem mirror blocks of brain and peripheral organ samples from COVID-19 cases. Nanoscale microscopy, single-cell RNAseq and analysis of inflammatory and metabolic signatures revealed that focal loss of microglial P2Y12R occurs at sites of virus-associated vascular inflammation together with dysregulated microglia-vascular-astrocyte interactions, Cx3Cr1-fractalkine axis deficits and mitochondrial failure in severely affected medullary autonomic nuclei, and other brain areas. Microglial dysfunction occurs at sites of excessive synapse- and myelin phagocytosis and loss of glutamatergic terminals. These changes strongly correlate with the development of a generalized, but regionally heterogenous proinflammatory response across the brain related to interleukin-1 (IL-1), IL-6, and multiorgan virus load-related systemic inflammation via virus-sensing pattern recognition receptors (PRRs) and inflammasomes. Thus, SARS-CoV-2-induced central and systemic inflammation might lead to a primarily glio-vascular failure in the brain, promoting diverse neuropathologies through different, parallel mechanisms.

2024-11-18 | GSE234720 | GEO

Microglial pattern recognition via IL-33 promotes synaptic refinement in developing corticothalamic circuits in mice (ATACseq)

Project description:To determine the direct effect of IL-33 on microglial gene expression, we have bulk ATAC-sequenced cortical microglia 4 hours after IL-33 or vehicle i.c.v. injection.

2022-12-12 | GSE218424 | GEO

Microglial pattern recognition via IL-33 promotes synaptic refinement in developing corticothalamic circuits in mice (scRNAseq)

Project description:To determine the effect of IL-33 on microglial gene expression, we have scRNA-sequenced cortical microglia from ST2KO and WT mice 4 hours after IL-33 or vehicle i.c.v. injection.

2022-12-12 | GSE218427 | GEO

Microglial pattern recognition via IL-33 promotes synaptic refinement in developing corticothalamic circuits in mice (bulk RNA-seq)

Project description:To determine the direct effect of IL-33 on microglial gene expression, we have bulk RNA-sequenced cortical microglia 4 hours after IL-33 or vehicle i.c.v. injection.

2022-12-12 | GSE218369 | GEO

Microglial pattern recognition via IL-33 promotes synaptic refinement in developing corticothalamic circuits in mice (H3K27ac ChIP-seq)

Project description:To determine the direct effect of IL-33 on microglial gene expression, we have H3K27ac ChIP-sequenced cortical microglia 4 hours after IL-33 or vehicle i.c.v. injection.

2022-12-12 | GSE218426 | GEO

Microglial pattern recognition via IL-33 promotes synaptic refinement in developing corticothalamic circuits in mice (FOS ChIP-seq)

Project description:To determine whether FOS is involved in the IL-33 microglial gene expression response, we have FOS ChIP-sequenced cortical microglia 4 hours after IL-33 i.c.v. injection.

2022-12-12 | GSE218425 | GEO

Integrative molecular and clinical profiling of acral melanoma links focal amplification of chr22q11.21 to metastasis

Project description:Integrative molecular and clinical profiling of acral melanoma links focal amplification of chr22q11.21 to metastasis

| PRJNA782616 | ENA

The VCAM1–ApoE pathway directs microglial chemotaxis and alleviates Alzheimer’s disease pathology

Project description:In Alzheimer’s disease (AD), sensome receptor dysfunction impairs microglial danger-associated molecular pattern (DAMP) clearance and exacerbates disease pathology. While extrinsic signals including interleukin-33 (IL-33) can restore microglial DAMP clearance, it remains largely unclear how the sensome receptor(s) is regulated and interacts with DAMP during phagocytic clearance. Here, we show that IL-33 induces VCAM1 in microglia, which promotes microglial chemotaxis toward amyloid-beta (Aβ) plaque-associated ApoE, and leads to Aβ clearance. We show that IL-33 stimulates a chemotactic state in microglia, characterized by Aβ-directed migration. Functional screening identified that VCAM1 directs microglial Aβ chemotaxis by sensing Aβ plaque-associated ApoE. Moreover, we found that disrupting VCAM1–ApoE interaction abolishes microglial Aβ chemotaxis, resulting in decreased microglial clearance of Aβ. In patients with AD, higher cerebrospinal fluid levels of soluble VCAM1 were correlated with impaired microglial Aβ chemotaxis. Together, our findings demonstrate that promoting VCAM1–ApoE-dependent microglial functions ameliorates AD pathology.

2023-07-18 | GSE208006 | GEO

CSF-1 and IL-34 drive distinct microglial programs in the brain tissue

Project description:CSF-1 and IL-34 drive distinct microglial programs in the brain tissue

| PRJNA551258 | ENA

IL-33-PU.1 transcriptome reprogramming drives functional state transition and clearance activity of microglia in Alzheimer’s disease

Project description:Impairment of microglial clearance activity contributes to beta-amyloid (Aβ) pathology in Alzheimer disease (AD). While the transcriptome profile of microglia directs microglial functions, how the microglial transcriptome can be regulated to alleviate AD pathology is largely unknown. Here, we show that injection of interleukin (IL)-33 in an AD transgenic mouse model ameliorates Aβ pathology by reprogramming microglial epigenetic and transcriptomic profiles to induce a microglial subpopulation with enhanced phagocytic activity. These IL-33–responsive microglia (IL-33RM) express distinct transcriptome signature, highlighted by major histocompatibility complex class II genes, and restored homeostatic signature genes. IL-33–induced remodeling of chromatin accessibility and PU.1 transcription factor binding at the signature genes of IL-33RM control their transcriptome reprogramming. Specifically, disrupting PU.1–DNA interaction abolishes the microglial state transition and Aβ clearance induced by IL-33. Thus, we define a PU.1-dependent transcriptional pathway that drives the IL-33–induced functional state transition of microglia, resulting in enhanced Aβ clearance.

2020-05-01 | GSE147495 | GEO