NOTCH2 disrupts the synovial fibroblast identity and the inflammatory response of epiphyseal chondrocytes
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ABSTRACT:
PROVIDER: PRJNA1241286 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR32840231_1.fastq.gz | Fastqsanger.gz | |||
| SRR32840231_2.fastq.gz | Fastqsanger.gz | |||
| SRR32840234_1.fastq.gz | Fastqsanger.gz | |||
| SRR32840234_2.fastq.gz | Fastqsanger.gz |
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Project description:Notch signaling plays a fundamental role in the inflammatory response and has been linked to the pathogenesis of osteoarthritis in murine models of the disease and in humans, but the mechanisms are poorly understood. We examined the effects of NOTCH2 in chondrocytes from Notch2tm1.1Ecan mice harboring a NOTCH2 gain-of-function mutation and from R26-NICD2 mice, a conditional gain-of-NOTCH2 function model, expressing the NOTCH2 intracellular domain (NICD2) from the Rosa26 locus. Bulk RNA-Sequencing (Seq) revealed increased expression of pathways associated with the phagosome, the role of osteoclasts in rheumatoid arthritis signaling and pulmonary fibrosis signaling in Notch2tm1.1Ecan and NICD2-expressing cultures. Collagen degradation was enhanced in Notch2tm1.1Ecan chondrocytes and the osteoarthritis pathway in NICD2-expressing cells. Single cell (sc)RNA-Seq analyzed 7,845 control and 7,141 Notch2tm1.1Ecan cells and used to define cell clusters. The more prevalent ones were constituted by limb mesenchyme, chondrogenic cells and fibroblasts including articular synovial fibroblasts. Pseudotime trajectory finding revealed a good association among clusters in control cultures, but this was disrupted in the articular/synovial cluster from Notch2tm1.1Ecan mice. scRNA-Seq of R26-NICD2 mice analyzed 9,957 cells in control and 9,924 in NICD2-expressing cultures. Neither the cluster distribution nor the pseudotime trajectory analysis revealed substantial differences between NIDC2-expressing and control cells except for an altered progression in an undefined cluster in NICD2-expressing cells. In conclusion, NOTCH2 enhances the activity of pathways associated with inflammation in epiphyseal chondrocytes and disrupts the transcriptome profile of articular/synovial fibroblasts.
2025-06-25 | GSE292806 | GEO
Project description:Notch signaling plays a fundamental role in the inflammatory response and has been linked to the pathogenesis of osteoarthritis in murine models of the disease and in humans, but the mechanisms are poorly understood. We examined the effects of NOTCH2 in chondrocytes from Notch2tm1.1Ecan mice harboring a NOTCH2 gain-of-function mutation and from R26-NICD2 mice, a conditional gain-of-NOTCH2 function model, expressing the NOTCH2 intracellular domain (NICD2) from the Rosa26 locus. Bulk RNA-Sequencing (Seq) revealed increased expression of pathways associated with the phagosome, the role of osteoclasts in rheumatoid arthritis signaling and pulmonary fibrosis signaling in Notch2tm1.1Ecan and NICD2-expressing cultures. Collagen degradation was enhanced in Notch2tm1.1Ecan chondrocytes and the osteoarthritis pathway in NICD2-expressing cells. Single cell (sc)RNA-Seq analyzed 7,845 control and 7,141 Notch2tm1.1Ecan cells and used to define cell clusters. The more prevalent ones were constituted by limb mesenchyme, chondrogenic cells and fibroblasts including articular synovial fibroblasts. Pseudotime trajectory finding revealed a good association among clusters in control cultures, but this was disrupted in the articular/synovial cluster from Notch2tm1.1Ecan mice. scRNA-Seq of R26-NICD2 mice analyzed 9,957 cells in control and 9,924 in NICD2-expressing cultures. Neither the cluster distribution nor the pseudotime trajectory analysis revealed substantial differences between NIDC2-expressing and control cells except for an altered progression in an undefined cluster in NICD2-expressing cells. In conclusion, NOTCH2 enhances the activity of pathways associated with inflammation in epiphyseal chondrocytes and disrupts the transcriptome profile of articular/synovial fibroblasts.
2025-06-25 | GSE292807 | GEO
Project description:NOTCH2 disrupts the synovial fibroblast identity and the inflammatory response of epiphyseal chondrocytes [scRNA-Seq]
| PRJNA1241287 | ENA
Project description:To investigate the role of Notch2 in the inflammatory response in chondrocytes, we cultured primary chondrocytes derived from wild type and Notch2 mutant mice and treated TNFalpha or vehicle. We then performed gene expression profiling analysis using data obtained from RNA-seq of wild type and Notch2 mutant chondrocytes.
2023-10-16 | GSE224255 | GEO
Project description:Effect of Notch2 in chondrocytes
| PRJNA930413 | ENA
Project description:Longitudinal bone growth depends upon the execution of an intricate series of cellular activities by epiphyseal growth plate chondrocytes. In order to better understand these coordinated events, microarray analysis was used to compare gene expression in chondrocytes isolated from the proliferative and hypertrophic zones of the avian growth plate. In this experiment we compared pooled samples of proliferative and hypertrophic chondrocytes isolated from the chick growth plate. The expression of 745 genes was found to differ 3-fold or greater at the 0.05 level of probability. Experiment Overall Design: We examined 8 samples using arrays: 4 from proliferative and 4 from hypertrophic chondrocytes.
2009-10-23 | E-GEOD-18568 | biostudies-arrayexpress
Project description:Longitudinal bone growth depends upon the execution of an intricate series of cellular activities by epiphyseal growth plate chondrocytes. In order to better understand these coordinated events, microarray analysis was used to compare gene expression in chondrocytes isolated from the proliferative and hypertrophic zones of the avian growth plate. In this experiment we compared pooled samples of proliferative and hypertrophic chondrocytes isolated from the chick growth plate. The expression of 745 genes was found to differ 3-fold or greater at the 0.05 level of probability.
2009-10-16 | GSE18568 | GEO
Project description:We used human fetal bone marrow-derived mesenchymal stromal cells (hfMSCs) differentiating towards chondrocytes as an alternative model for the human growth plate (GP). Our aims were to study gene expression patterns associated with chondrogenic differentiation to assess whether chondrocytes derived from hfMSCs are a suitable model for studying the development and maturation of the GP. hfMSCs efficiently formed hyaline cartilage in a pellet culture in the presence of TGFB3 and BMP6. Microarray and principal component analysis were applied to study gene expression profiles during chondrogenic differentiation. A set of 232 genes was found to correlate with in vitro cartilage formation. Several identified genes are known to be involved in cartilage formation and validate the robustness of the differentiating hfMSC model. KEGG pathway analysis using the 232 genes revealed 9 significant signaling pathways correlated with cartilage formation. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development. To determine the progression of growth plate cartilage formation, we compared the gene expression profile of differentiating hfMSCs with previously established expression profiles of epiphyseal GP cartilage. As differentiation towards chondrocytes proceeds, hfMSCs gradually obtain a gene expression profile resembling epiphyseal GP cartilage. We visualized the differences in gene expression profiles as protein interaction clusters and identified many protein clusters that are activated during the early chondrogenic differentiation of hfMSCs showing the potential of this system to study GP development. RNA fhMSCs of chondrogenically differentiating fhMSCs was isolated at week, 0, 1, 2, 3, 4 and 5. Moreover, RNA of 4 human growth plates from was isolated.
2013-04-22 | E-GEOD-40942 | biostudies-arrayexpress
Project description:Knee osteoarthritis (KOA), as a degenerative multifactorial disease, affects the quality of life and mental health of patients, and also brings a huge socioeconomic burden. Treating synovitis have shown promise as anti-inflammatory therapeutics in mitigating OA symptoms and disease progression. Here, by analysing synovial single-cell sequencing (scRNA-seq) data from KOA, we found that synovial fibroblasts (FLS) in OA synovium showed a distinct pro-inflammatory phenotype. We collected synovial tissue from patients with clinical OA as well as from healthy donors, and histological examination was consistent with findings in scRNA-seq. Inspired by recent cross-tissue fibroblast lineage studies, we identified by sequencing that healthy FLS in synovial tissues share transcriptome-level similarities with dermal fibroblasts (DFb). Subsequently, we revealed the local as well as systemic distribution of intra-articular injected DFbs by constructing/extracting two types of rat fibroblasts (luciferase DFbs as well as GFP DFbs). The results demonstrate that DFbs can be locally retained in the synovium for up to three weeks following targeted engrafting on it. And intra-articular injection does not result in DFbs migration to vital organs or the occurrence of histological changes in these organs. A rat model of KOA was constructed by anterior cruciate ligament transection (ACLT) in order to study the therapeutic effect of DFbs on KOA. After injection, the rats showed improvement in painful gait. In addition, histological as well as imaging results showed reduced synovitis and improvement in articular cartilage. Finally we verified the protective effect of DFbs on cytokine-stimulated chondrocytes in a co-culture system.
2025-01-13 | GSE285941 | GEO
Project description:Increased interleukin (IL)-17A has been identified in joints affected by osteoarthritis (OA), but it is unclear how IL-17A, and its family members IL-17AF and IL-17F, can contribute to human OA pathophysiology. Therefore, we aimed to evaluate the gene expression and signalling pathway activation effects of the different IL-17 family members in chondrocytes and fibroblasts derived from cartilage and synovium of patients with end-stage knee OA. Chondrocytes and synovial fibroblasts derived from end-stage OA patients were treated with IL-17A, IL-17AF, or IL-17F, and gene expression was assessed with bulk RNA-Seq. Hallmark pathway analysis showed that IL-17 cytokines regulated several OA pathophysiology-related pathways including immune-, angiogenesis-, and complement-pathways in both chondrocytes and synovial fibroblasts derived from end-stage OA patients. While overall IL-17A induced the strongest transcriptional response, followed by IL-17AF and IL-17F, not all genes followed this pattern. Disease-Gene Network analysis revealed that IL-17A-related changes in gene expression in these cells are associated with experimental arthritis, knee arthritis, and musculoskeletal disease gene-sets. In conclusion, the association of IL-17-induced transcriptional changes with arthritic gene-sets supports a role for IL-17A in OA pathophysiology.
2021-06-02 | GSE171952 | GEO