A single cell transcriptional atlas of early synovial joint development
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ABSTRACT:
PROVIDER: PRJNA638016 | ENA |
REPOSITORIES: ENA
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Project description:Synovial joint development begins with the formation of the interzone, a region of condensed mesenchymal cells at the site of the prospective joint. Recently, lineage tracing strategies have revealed that Gdf5-lineage cells native to and from outside the interzone contribute to most, if not all, of the major joint components. However, there is limited knowledge of the specific transcriptional and signaling programs that regulate interzone formation and fate diversification of synovial joint constituents. To address this, we have performed single cell RNA-Seq analysis of 7,329 synovial joint progenitor cells from the developing murine knee joint from E12.5 to E15.5. By using a combination of computational analytics, in situ hybridization, and in vitro characterization of prospectively isolated populations, we have identified the transcriptional profiles of the major developmental paths for joint progenitors. Our freely available single cell transcriptional atlas will serve as a resource for the community to uncover transcriptional programs and cell interactions that regulate synovial joint development.
2020-06-23 | GSE151985 | GEO
Project description:Synovial joint development begins with the formation of the interzone, a region of condensed mesenchymal cells at the site of the prospective joint. Recently, lineage-tracing strategies have revealed that Gdf5-lineage cells native to and from outside the interzone contribute to most, if not all, of the major joint components. However, there is limited knowledge of the specific transcriptional and signaling programs that regulate interzone formation and fate diversification of synovial joint constituents. To address this, we have performed single cell RNA-Seq analysis of 7329 synovial joint progenitor cells from the developing murine knee joint from E12.5 to E15.5. By using a combination of computational analytics, in situ hybridization and in vitro characterization of prospectively isolated populations, we have identified the transcriptional profiles of the major developmental paths for joint progenitors. Our freely available single cell transcriptional atlas will serve as a resource for the community to uncover transcriptional programs and cell interactions that regulate synovial joint development.
| S-EPMC7390639 | biostudies-literature
Project description:Synovial fibroblasts contribute to the inflammatory temporomandibular joint under pathogenic stimuli. Synovial fibroblasts and T cells participate in the perpetuation of joint inflammation in a mutual activation feedback, via secretion of cytokines and chemokines that stimulate each other. IL-17 is an inflammatory cytokine produced primarily by Th17 cells that plays critical roles in the pathogenesis of numerous autoimmune and inflammatory diseases. Here, we investigated the roles of IL-17A in temporomandibular joint disorders (TMD) by using genome-wide analysis of synovial fibroblasts isolated from patients with TMD. We analyzed the gene expression profiles of synovial fibroblasts that were treated with or without IL-17A. IL-17 induced gene expression in synovial fibroblasts from human temporomandibular joint was measured at 4 hours after treated with IL-17A (10 ng/ml) and untreated control samples. This experiment used one donor sample.
2015-11-05 | E-GEOD-74668 | biostudies-arrayexpress
Project description:Adult mammalian synovial joints have limited regenerative capacity, where injuries heal with mechanically inferior fibrotic joint tissues. Here we developed a unilateral whole-joint resection model in adult zebrafish to advance our understanding of how to stimulate regrowth of native synovial joint tissues. Using single-cell RNA sequencing, we profile RNA expression from live-sorted jaw joint cells throughout the time course of joint regeneration (1 to 70 days-post-joint-resection (dpjr)). Our findings reveal latent molecular and cellular programs within the adult skeleton that are deployed to regenerate a complex joint with lubricated articular cartilage.
2024-12-16 | GSE283763 | GEO
Project description:Synovial fibroblasts contribute to the inflammatory temporomandibular joint under pathogenic stimuli. Synovial fibroblasts and T cells participate in the perpetuation of joint inflammation in a mutual activation feedback, via secretion of cytokines and chemokines that stimulate each other. IL-17 is an inflammatory cytokine produced primarily by Th17 cells that plays critical roles in the pathogenesis of numerous autoimmune and inflammatory diseases. Here, we investigated the roles of IL-17A in temporomandibular joint disorders (TMD) by using genome-wide analysis of synovial fibroblasts isolated from patients with TMD. We analyzed the gene expression profiles of synovial fibroblasts that were treated with or without IL-17A.
2015-11-05 | GSE74668 | GEO
Project description:Small RNA isolated from synovial fluid of the metacarpophalangeal joints of horses. Horses either had minimal signs of osteoarthritis based on macroscopic and microscopic joint scoring or early (mild) osteoarthritis. Differential expression of small non-coding RNAs was undertaken.
2020-06-30 | E-MTAB-8409 | biostudies-arrayexpress
Project description:Macrophages (MΦs) are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis 1. However, both the exact origin and role of MΦs during inflammatory joint disease remain unclear. Here, we used multiple fate-mapping approaches in conjunction with 3D-light-sheet fluorescence microscopy and single cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of MΦ subsets within the healthy and inflamed joint and subsequently studied their roles during arthritis. This approach revealed dynamic membrane-like structures consisting of a distinct population of CX3CR1+ tissue-resident MΦs that formed an internal immunological barrier at the synovial lining and physically secluded the joint. Barrier-forming MΦs displayed features otherwise typical of epithelial cells, and maintained their numbers through a pool of locally proliferating CX3CR1- mononuclear cells embedded into the synovial tissue. Unlike recruited monocyte-derived MΦs, which actively contributed to joint inflammation, such epithelial-like CX3CR1+ lining MΦs restricted the inflammatory reaction by providing a tight junction-mediated shield for intra-articular structures. Our data thus reveal an unexpected functional diversification among synovial MΦs and have important implications for the general role of MΦs in health and disease.
2019-08-07 | GSE134286 | GEO
Project description:Macrophages (MΦs) are considered to contribute to chronic inflammatory diseases such as rheumatoid arthritis 1. However, both the exact origin and role of MΦs during inflammatory joint disease remain unclear. Here, we used multiple fate-mapping approaches in conjunction with 3D-light-sheet fluorescence microscopy and single cell RNA sequencing to perform a comprehensive spatiotemporal analysis of the composition, origin and differentiation of MΦ subsets within the healthy and inflamed joint and subsequently studied their roles during arthritis. This approach revealed dynamic membrane-like structures consisting of a distinct population of CX3CR1+ tissue-resident MΦs that formed an internal immunological barrier at the synovial lining and physically secluded the joint. Barrier-forming MΦs displayed features otherwise typical of epithelial cells, and maintained their numbers through a pool of locally proliferating CX3CR1- mononuclear cells embedded into the synovial tissue. Unlike recruited monocyte-derived MΦs, which actively contributed to joint inflammation, such epithelial-like CX3CR1+ lining MΦs restricted the inflammatory reaction by providing a tight junction-mediated shield for intra-articular structures. Our data thus reveal an unexpected functional diversification among synovial MΦs and have important implications for the general role of MΦs in health and disease
2019-08-07 | GSE134420 | GEO
Project description:Mucopolysaccharidosis I is a lysosomal storage disorder characterized by deficient alpha-L-iduronidase activity, leading to abnormal accumulation of glycosaminoglycans in cells and tissues. Synovial joint disease is prevalent and significantly reduces patient quality of life. There is a critical need for improved understanding of joint disease pathophysiology in MPS I, including specific biomarkers to predict and monitor joint disease progression, and response to treatment. The objective of this study was to leverage the naturally-occurring MPS I canine model and undertake an unbiased proteomic screen to identify systemic biomarkers predictive of local joint disease in MPS I. Synovial fluid and serum samples were collected from MPS I and healthy dogs at 12 months-of-age, and protein abundance characterized using LC MS/MS. Stifle joints were evaluated postmortem using magnetic resonance imaging (MRI) and histology. Proteomics identified 40 proteins for which abundance was significantly correlated between serum and synovial fluid, including markers of inflammatory joint disease and lysosomal dysfunction. Elevated expression of three biomarker candidates, matrix metalloproteinase 19, inter-alpha-trypsin inhibitor heavy-chain 3 and alpha-1-microglobulin, was confirmed in MPS I cartilage, and serum abundance of these molecules was found to correlate with MRI and histological degenerative grades. The candidate biomarkers identified in this study have the potential to improve patient care by facilitating minimally-invasive, specific assessment of joint disease severity, progression and response to therapeutic intervention.
2024-05-22 | PXD037130 | Pride
Project description:We report the 3D chromatin organization of the 3.4Mb DACT2-SMOC2 locus generated for interphalangeal interzone and phalange, tissues collected during synovial joint formation. The interzone and phalange samples have been dissected from developing hindlimb digits of the chicken embryo at Hamilton Hamburger stage 32 (HH32). Collected material has been processed using the Targeted Chromatin Capture protocol optimized for the 1mln cell. Generation of the T2C-interaction maps has revealed the 3D chromatin architecture of the DACT2-SMOC2 locus in the interzone and phalange tissues as well as identified potential candidate enhancers located in spatial proximity of DACT2 and SMOC2 gene promoters. We report the ChIPseq derived Candidate Enhancer (CE) atlas generated for interphalangeal interzone and phalange, tissues collected during synovial joint formation. Three replicates for interzone and three replicated for phalange were immunoprecipitated (IP) with the H3K27ac antibodies. Also, two replicates for interzone and two replicates for phalange were immunoprecipitated with H3K4me1 antibodies. The IP samples for both histone marks were sequenced and used for annotation of CEs. Further, the CEs were functionally annotated. In parallel, the total RNA for three interzone and three phalange replicates was isolated and mRNA sequencing libraries were constructed. Next the identification of differentially expressed genes (DEGs) and integrative analysis of DEGs and CEs was performed.
2024-07-01 | GSE210108 | GEO