Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE139552 | GEO | 2020/11/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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: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 | 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 [smarter-seq]

2020-11-22 | GSE139549 | GEO

Fully defined human pluripotent stem cell-derived microglia and tri-culture system model C3 production in Alzheimer's disease.

Project description:Aberrant inflammation in the CNS has been implicated as a major player in the pathogenesis of human neurodegenerative disease. We developed a new approach to derive microglia from human pluripotent stem cells (hPSCs) and built a defined hPSC-derived tri-culture system containing pure populations of hPSC-derived microglia, astrocytes, and neurons to dissect cellular cross-talk along the neuroinflammatory axis in vitro. We used the tri-culture system to model neuroinflammation in Alzheimer's disease with hPSCs harboring the APPSWE+/+ mutation and their isogenic control. We found that complement C3, a protein that is increased under inflammatory conditions and implicated in synaptic loss, is potentiated in tri-culture and further enhanced in APPSWE+/+ tri-cultures due to microglia initiating reciprocal signaling with astrocytes to produce excess C3. Our study defines the major cellular players contributing to increased C3 in Alzheimer's disease and presents a broadly applicable platform to study neuroinflammation in human disease.

| S-EPMC8382543 | biostudies-literature

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 [smarter-seq]

| PRJNA580240 | ENA

A fully defined static suspension culture system for large-scale human embryonic stem cell production.

Project description:Human embryonic stem cells (hESCs) play an important role in regenerative medicine due to their potential to differentiate into various functional cells. However, the conventional adherent culture system poses challenges to mass production of high-quality hESCs. Though scientists have made many attempts to establish a robust and economical hESC suspension culture system, there are existing limitations, including suboptimal passage methods and shear force caused by dynamic stirring. Here, we report on an efficient large-scale culture system, which enables long-term, GMP grade, single-cell inoculation, and serial expansion of hESCs with a yield of about 1.5 × 109 cells per 1.5-L culture, while maintaining good pluripotency. The suspension culture system was enlarged gradually from a 100-mm dish to a 1.8-L culture bag with methylcellulose involvement to avoid sphere fusion. Under the optimal experimental protocol, this 3D system resolves current problems that limit mass production and clinical application of hESCs, and thus can be used in commercial-level hESC production for cell therapy and pharmaceutics screening in the future.

| S-EPMC6117302 | biostudies-literature

A novel composition for the culture of human adipose stem cells which includes complement C3.

Project description:Adipose tissue is an easily accessible and abundant source of stem cells. Adipose stem cells (ASCs) are currently being researched as treatment options for repair and regeneration of damaged tissues. The standard culture conditions used for expansion of ASCs contain fetal bovine serum (FBS) which is undefined, could transmit known and unknown adventitious agents, and may cause adverse immune reactions. We have described a novel culture condition which excludes the use of FBS and characterised the resulting culture. Human ASCs were cultured in the novel culture medium, which included complement protein C3. These cultures, called C-ASCs, were compared with ASCs cultured in medium supplemented with FBS. Analysis of ASCs for surface marker profile, proliferation characteristics and differentiation potential indicated that the C-ASCs were similar to ASCs cultured in medium containing FBS. Using a specific inhibitor, we show that C3 is required for the survival of C-ASCs. This novel composition lends itself to being developed into a defined condition for the routine culture of ASCs for basic and clinical applications.

| S-EPMC2993860 | biostudies-literature

Surface-engineered substrates for improved human pluripotent stem cell culture under fully defined conditions.

Project description:The current gold standard for the culture of human pluripotent stem cells requires the use of a feeder layer of cells. Here, we develop a spatially defined culture system based on UV/ozone radiation modification of typical cell culture plastics to define a favorable surface environment for human pluripotent stem cell culture. Chemical and geometrical optimization of the surfaces enables control of early cell aggregation from fully dissociated cells, as predicted from a numerical model of cell migration, and results in significant increases in cell growth of undifferentiated cells. These chemically defined xeno-free substrates generate more than three times the number of cells than feeder-containing substrates per surface area. Further, reprogramming and typical gene-targeting protocols can be readily performed on these engineered surfaces. These substrates provide an attractive cell culture platform for the production of clinically relevant factor-free reprogrammed cells from patient tissue samples and facilitate the definition of standardized scale-up friendly methods for disease modeling and cell therapeutic applications.

| S-EPMC3219112 | biostudies-literature

Biologically relevant laminin as chemically defined and fully human platform for human epidermal keratinocyte culture.

Project description:The current expansion of autologous human keratinocytes to resurface severe wound defects still relies on murine feeder layer and calf serum in the cell culture system. Through our characterization efforts of the human skin basement membrane and murine feeder layer 3T3-J2, we identified two biologically relevant recombinant laminins-LN-511 and LN-421- as potential candidates to replace the murine feeder. Herein, we report a completely xeno-free and defined culture system utilizing these laminins which enables robust expansion of adult human skin keratinocytes. We demonstrate that our laminin system is comparable to the 3T3-J2 co-culture system in terms of basal markers' profile, colony-forming efficiency and the ability to form normal stratified epidermal structure in both in vitro and in vivo models. These results show that the proposed system may not only provide safer keratinocyte use in the clinics, but also facilitate the broader use of other cultured human epithelial cells in regenerative medicine.

| S-EPMC6207750 | biostudies-literature

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