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CRISPR screen identified CLEC16A suppresses astrocyte inflammasome-involved pathology via mitophagy: EAE study

ABSTRACT: CLEC16A conditional knockout using GFAP-Cre

ORGANISM(S): Mus musculus

PROVIDER: GSE189029 | GEO | 2023/11/09

REPOSITORIES: GEO

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CRIPSR screen identified CLEC16A suppresses astrocyte inflammasome-involved pathology via mitophagy (Single Cell Dataset)

Project description:Astrocytes promote neuroinflammation and neurodegeneration in multiple sclerosis (MS) through cell-intrinsic activities, and also via their ability to recruit and activate other cell types. Here, we report the results of a genome-wide CRISPR-based forward genetic screen investigating regulators of astrocyte proinflammatory responses, which identified CLEC16A, a gene linked to MS susceptibility, as a suppressor of NF-B signaling. Gene and small molecule perturbation studies in mouse primary and human embryonic stem cell-derived astrocytes in combination with multi-omic analyses established that CLEC16A promotes mitophagy, limiting mitochondrial dysfunction and the accumulation of mitochondrial products that activate NF-κB, the NLRP3 inflammasome and gasdermin D. Astrocytespecific Clec16a inactivation increased NF-κB, NLRP3 and gasdermin D activation in vivo, worsening experimental autoimmune encephalomyelitis, a mouse model of MS. Moreover, we detected disrupted mitophagic capacity and gasdermin D activation in astrocytes in samples from individuals with MS. These findings identify CLEC16A as a suppressor of astrocyte pathologic responses and a candidate therapeutic target in MS.

2024-12-03 | GSE283395 | GEO

CRIPSR screen identified CLEC16A suppresses astrocyte inflammasome-involved pathology via mitophagy: human in vitro study

Project description:CLEC16A knocked down human embryonic stem cell (hESC) derived astrocytes

2023-11-09 | GSE189028 | GEO

CRISPR screen identified CLEC16A suppresses astrocyte inflammasome-involved pathology via mitophagy: EAE study

Project description:CRISPR screen identified CLEC16A suppresses astrocyte inflammasome-involved pathology via mitophagy: EAE study

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CRIPSR screen identified CLEC16A suppresses astrocyte inflammasome-involved pathology via mitophagy

Project description:CRIPSR screen identified CLEC16A suppresses astrocyte inflammasome-involved pathology via mitophagy

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CRIPSR screen identified CLEC16A suppresses astrocyte inflammasome-involved pathology via mitophagy

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-11-09 | GSE189030 | GEO

CRIPSR screen identified CLEC16A suppresses astrocyte inflammasome-involved pathology via mitophagy (Single Cell Dataset)

Project description:CRIPSR screen identified CLEC16A suppresses astrocyte inflammasome-involved pathology via mitophagy (Single Cell Dataset)

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CRIPSR screen identified CLEC16A suppresses astrocyte inflammasome-involved pathology via mitophagy: human in vitro study

Project description:CRIPSR screen identified CLEC16A suppresses astrocyte inflammasome-involved pathology via mitophagy: human in vitro study

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Microarray analysis of the astrocyte transcriptome in the ageing brain: relationship to Alzheimer's pathology and ApoE genotype

Project description:Astrocyte dysfunction impacts their normal function, including neuronal support, thereby contributing to neurodegenerative pathologies including Alzheimer's disease (AD). Therefore to understand the role of astrocytes in the pathogenesis of age-related disorders we analysed the gene expression profile of astrocytes with respect to Alzheimer-type pathology. The aim of the present study was to combine immuno-LCM and microarray analysis to characterise the astrocyte transcriptome at different Braak stages, and with respect to ApoE genotype, in post-mortem human temporal cortex sampled dervied from the Medical Research Council Cognitive Function and Ageing Study (MRC-CFAS). GFAP-positive astrocytes were isolated from age, sex and brain pH-matched cases derived from the MRC-CFAS cohort, using immuno laser capture microdissection. The extracted RNA was amplified and applied to HGU133 Plus 2.0 Affymetrix gene arrays. Genes were considered differentially expressed if they showed a minimum 1.5 fold change at p<0.02 in all 6 individual cases in each stage of pathology [18 cases in total: 6 cases Braak stages I-II (3 cases carried at least one ApoE epsilon4 allele and 3 were ApoEe4 negative); 6 cases Braak stages III-IV (3 ApoEe4 positive and 3 ApoEe4 negative; 6 cases Braak stages V-VI (3 ApoEe4 positive and 3 ApoEe4 negative)]. keywords: human GFAP-positive astrocytes

2011-06-01 | E-GEOD-29652 | biostudies-arrayexpress

Dihydromyricetin suppresses endothelial NLRP3 inflammasome activation and attenuates atherogenesis by promoting mitophagy

Project description: Not available

| S-EPMC11370113 | biostudies-literature

Identification of genes associated with the astrocyte-specific gene Gfap during astrocyte differentiation

Project description:Chromosomes and genes are non-randomly arranged within the mammalian cell nucleus. Clustering of genes is of great significance in transcriptional regulation. However, the relevance of gene clustering in their expression during differentiation of neural precursor cells (NPCs) into astrocytes remains unclear. We performed a genome-wide enhanced circular chromosomal conformation capture (e4C) to screen genes associated with an astrocyte-specific gene, glial fibrillary acidic protein (Gfap), during astrocyte differentiation. We identified 13 genes that were specifically associated with Gfap and expressed in NPC-derived astrocytes. These results provide evidence for functional significance of gene clustering in transcriptional regulation during NPCs differentiation. comparison of NPCs vs LIF+ vs LIF- cells.

2015-02-20 | E-GEOD-66097 | biostudies-arrayexpress

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