Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Molecular reframing of fibroblasts during resolution of arthritis [scRNA]

ABSTRACT: Fibroblasts are key orchestrators of inflammation. Little is known whether these cells change phenotype during resolution of inflammation. We adopted a method to visualise fibroblast activation during inflammation in humans in vivo, which is based on a fibroblast activation protein (FAP) tracer detected by positron emission tomography (PET). While tracer accumulation was high in active arthritis, it decreased significantly after TNF- and IL-17A inhibition. Biopsy-based scRNA-seq analyses in experimental arthritis demonstrated that FAP signal reduction reflected a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalisation) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalisation). Spatial transcriptomics of human joints revealed that pro-resolving niches of CD200+DKK3+ fibroblasts clustered with innate lymphoid cells (ILC)2, whereas MMP3+/IL6+ fibroblasts were co-localised with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilised the ILC2 phenotype and induced resolution of arthritis via CD200/CD200R1 pathway. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.

ORGANISM(S): Mus musculus

PROVIDER: GSE228980 | GEO | 2024/01/16

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Molecular reframing of fibroblasts during resolution of arthritis [scRNA 2]

Project description:Fibroblasts are key orchestrators of inflammation. Little is known whether these cells change phenotype during resolution of inflammation. We adopted a method to visualise fibroblast activation during inflammation in humans in vivo, which is based on a fibroblast activation protein (FAP) tracer detected by positron emission tomography (PET). While tracer accumulation was high in active arthritis, it decreased significantly after TNF- and IL-17A inhibition. Biopsy-based scRNA-seq analyses in experimental arthritis demonstrated that FAP signal reduction reflected a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalisation) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalisation). Spatial transcriptomics of human joints revealed that pro-resolving niches of CD200+DKK3+ fibroblasts clustered with innate lymphoid cells (ILC)2, whereas MMP3+/IL6+ fibroblasts were co-localised with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilised the ILC2 phenotype and induced resolution of arthritis via CD200/CD200R1 pathway. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.

2024-01-16 | GSE228981 | GEO

Molecular reframing of fibroblasts during resolution of arthritis [Visium]

2024-01-16 | GSE228972 | GEO

Molecular reframing of fibroblasts during resolution of arthritis [RNA]

2024-01-16 | GSE228953 | GEO

Transcriptome analysis of synovial osteoprogenitor populations in mice with antigen-induced arthritis and non-immunized mice

Project description:The aim of this experiment was to analyze differences in gene expression between potential osteoprogenitor populations in synovial compartment of non-immunized mice and mice with antigen-induced arthritis (AIA). We analyzed transcriptome of TER119–CD31–CD45–CD51+CD200+CD105– cells from nonimmunized mice, TER119–CD31–CD45–CD51+CD200+CD105– cells from mice with arthritis, and TER119–CD31–CD45–CD51+CD200–CD105+ from mice with arthritis. Comparison between nonimmunized and arthritic mice served to determine changes in TER119–CD31–CD45–CD51+CD200+CD105–population induced by arthritis. Comparison of TER119–CD31–CD45–CD51+CD200+CD105– and TER119–CD31–CD45–CD51+CD200–CD105+ from mice with arthritis aimed to define transcriptomic differences between those two populations.

2020-05-05 | GSE148130 | GEO

Pathologically distinct fibroblast subsets drive inflammation and tissue damage in arthritis

Project description:The identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune mediated inflammatory diseases (IMIDs). Yet, despite their key role in disease, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue driven pathologies observed in IMIDs such as inflammation and damage . Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of FAPa+ synovial cells suppressed both inflammation and bone erosions in murine models of resolving and persistent arthritis. Single cell transcriptional analysis identified two distinct fibroblast subsets: FAPa+ THY1+ immune effector fibroblasts located in the synovial sub-lining, and FAPa+ THY1- destructive fibroblasts restricted to the synovial lining. When adoptively transferred into the joint, FAPa+ THY1- fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation whereas transfer of FAPa+ THY1+ fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell based therapies aimed at modulating inflammation and tissue damage.

2019-04-09 | GSE129451 | GEO

Pathologically distinct fibroblast subsets drive inflammation and tissue damage in arthritis

2019-06-03 | GSE129087 | GEO

Identification of novel natural substrates of fibroblast activation protein by differential degradomics and proteomics (TAILS dataset)

Project description:Fibroblast Activation Protein (FAP) is a cell-surface transmembrane-anchored anchored dimeric protease. This unique constitutively active serine protease has both dipeptidyl aminopeptidase and endopeptidase activities, and can hydrolyse post-proline bonds. FAP expression is very low in adult organs, but is greatly up regulated by activated fibroblasts in sites of tissue remodelling, including fibrosis, atherosclerosis, arthritis and tumours. Primary mouse embryonic fibroblasts (MEF) were isolated from FAP gene knockout (GKO) embryos, immortalised and then transduced to express either enzyme active or inactive FAP. The cell secretomes were analysed using degradomic and proteomic techniques. Terminal Amine Isotopic Labelling of Substrates based degradomics identified cleavage sites in collagens, many other extracellular matrix (ECM) and associated proteins, and lysyl oxidase-like-1, CCL2, IL13, C1qT6 and CSF-1 that were confirmed in vitro. In addition, differential metabolic labelling coupled with quantitative proteomic analysis also implicated FAP in ECM-cell interactions, as well as with coagulation and wound healing associated proteins. FAP GKO plasma exhibited slower that wildtype clotting times. This study greatly enhances the understanding of the roles of FAP through a significant expansion of the substrate repertoire of this protease and identifying downstream effects of its activity that support roles in pathological processes.

2018-12-19 | PXD004757 | Pride

Identification of novel natural substrates of fibroblast activation protein by differential degradomics and proteomics

2018-12-19 | PXD004754 | Pride

Illumina HumanmethylationEPIC array analysis in early synovial fibroblasts of RA patients before diagnosis

Project description:In the current study, we compared DNA methylation patterns using the Illumina 850k array technology between normal synovial fibroblasts and synovial fibroblasts from early (veRASF) and late stages of RA (estRASF) and transient, resolving arthritis (rSF). In doing so, we obtained a detailed view of changes in DNA methylation that occur during the development of RA from the earliest clinically apparent stages to established RA with its typical signs and symptoms.

2018-03-31 | E-MTAB-6582 | biostudies-arrayexpress

Illumina Humanmethylation450k array analysis in early synovial fibroblasts of RA patients before diagnosis

Project description:In the current study, we compared DNA methylation patterns using the Illumina 450k array technology between normal synovial fibroblasts and synovial fibroblasts from early (veRASF) and late stages of RA (estRASF) and transient, resolving arthritis (rSF). In doing so, we obtained a detailed view of changes in DNA methylation that occur during the development of RA from the earliest clinically apparent stages to established RA with its typical signs and symptoms.

2018-03-31 | E-MTAB-6581 | biostudies-arrayexpress

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