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Fully defined human PSC-derived microglia and tri-culture system reveals cell type specific potentiation of complement C3 production in a model of Alzheimer’s disease [smarter-seq]

ABSTRACT: Fully defined human PSC-derived microglia and tri-culture system reveals cell type specific potentiation of complement C3 production in a model of Alzheimer’s disease [smarter-seq]

PROVIDER: PRJNA580240 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10360244_1.fastq.gz	Fastqsanger.gz
	SRR10360244_2.fastq.gz	Fastqsanger.gz
	SRR10360245_1.fastq.gz	Fastqsanger.gz
	SRR10360245_2.fastq.gz	Fastqsanger.gz
	SRR10360246_1.fastq.gz	Fastqsanger.gz

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Fully defined human PSC-derived microglia and tri-culture system reveals cell type specific potentiation of complement C3 production in a model of Alzheimer’s disease [smarter-seq]

Project description:Aberrant inflammation in the central nervous system (CNS) has been implicated as a major player in the pathogenesis of human neurodegenerative disease. However, the specific contribution of each cell type to the neuroinflammatory axis in vivo remains unclear with species-specific differences in key signaling pathways further complicating the challenge. To assemble a fully human platform to study neuroinflammation, we first developed a novel approach to derive microglia from human pluripotent stem cells (hPSCs) that faithfully recapitulates microglial ontogeny as validated by single cell RNA-sequencing and stage-specific mapping onto datasets of developing mouse microglia. Using these cells, we build the first defined and completely hPSC-derived tri-culture system containing pure populations of hPSC-derived microglia, astrocytes, and neurons to dissect cellular crosstalk along the neuroinflammatory axis in vitro. We next used the tri-culture system to model neuroinflammation in Alzheimer’s Disease using hPSCs harboring the APPSWE+/+ mutation and their isogenic control. Our data reveal that production of complement C3, a protein that is increased under inflammatory conditions and implicated in synaptic loss, is potentiated under tri-culture conditions, and is further enhanced in APPSWE+/+ tri-cultures. Using cell type-specific ablation studies, we report that C3 potentiation is due to the presence of a neuroinflammatory loop in which microglia are the key initiators that activate reciprocal signaling with astrocytes to produce excess C3. Our study defines the major cellular players contributing to increased C3 in AD and presents a broadly applicable platform to study neuroinflammation in human disease.

2020-11-22 | GSE139549 | GEO

Fully defined human PSC-derived microglia and tri-culture system reveals cell type specific potentiation of complement C3 production in a model of Alzheimer’s disease [scRNA-seq]

2020-11-22 | GSE139550 | GEO

Fully defined human PSC-derived microglia and tri-culture system reveals cell type specific potentiation of complement C3 production in a model of Alzheimer’s disease

Project description:Fully defined human PSC-derived microglia and tri-culture system reveals cell type specific potentiation of complement C3 production in a model of Alzheimer’s disease

| PRJNA580239 | ENA

Fully defined human PSC-derived microglia and tri-culture system reveals cell type specific potentiation of complement C3 production in a model of Alzheimer’s disease [scRNA-seq]

Project description:Fully defined human PSC-derived microglia and tri-culture system reveals cell type specific potentiation of complement C3 production in a model of Alzheimer’s disease [scRNA-seq]

| PRJNA580245 | ENA

Fully defined human PSC-derived microglia and tri-culture system reveals cell type specific potentiation of complement C3 production in a model of Alzheimer’s disease

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

2020-11-21 | GSE139552 | GEO

PSC-IBD mucosal biology

Project description:Comparative colonic mucosal transcriptomics of 10 patients with PSC-IBD, 10 UC and 10 Healthy controls

2019-09-01 | E-MTAB-7915 | biostudies-arrayexpress

PSC-IBD mucosal biology

Project description:PSC-IBD mucosal biology

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PSC-IBD mucosal omics

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SMARTer single cell total RNA sequencing

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Proteomic analysis of serum EVs derived from PSC, CCA and PSC-CCA patients

Project description:Cholangiocarcinomas (CCAs) are heterogeneous biliary cancers with dismal prognosis. Their etiologies remain mostly unclear, although primary sclerosing cholangitis (PSC) is a well-known risk factor. There is an urgent need of accurate non-invasive biomarkers for early CCA diagnosis and to predict patient´s prognosis, which may improve their clinical management and outcome. Here, by high-throughput proteomic analysis of serum extracellular vesicles (EVs), we identified diagnostic and/or prognostic biomarkers specific for CCAs in patients with PSC, and others common to all CCA subtypes. Bulk RNA tissue transcriptomic data revealed that these biomarkers are predominantly expressed in hepatobiliary tissues, being expressed in different liver cell types. Furthermore, single-cell RNAseq (scRNA-seq) analysis revealed that the expression of these biomarkers was preferentially found in malignant cholangiocytes within CCA tumors. In summary, these results highlight the potential of serum EVs to reflect cancer presence, especially for difficult-to-diagnose malignancies, including CCA."

2023-07-20 | PXD026197 | Pride

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