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Multi-organ single cell analysis of a mouse model of collagen-induced arthritis [subseries1]

ABSTRACT: Prioratization of disease associated mechanisms in immune-mediated inflammatory diseases (IMIDs) is complicated by altered interactions across multiple organs and cell types. We have adressed these challenges by analyzing a multi-organ multicellular disease model (MO-MCDM) of a mouse IMID model, namely collagen-induced arthritis (CIA). For all the five organs (joint, lung, muscle, skin, and spleen) we found highly complex and heterogenous expression changes due to disease, although, macroscopic and microscopic signs of inflammation could only be seen in joints. Based on the MO-MCDM, predicted molecular interactions within and between organs could be identified. The model supported that inflammation was switched on or off in different organs, by an altered balande between pro- and anti-inflammatory upstream regulators and downstream pathways. This on/off switch was validated in human IMIDs, by analyses of publically available data from 32 different samples of 10 different IMIDs. Additionally, it showed consistency with a general characteristic of both CIA and human IMIDs, namely variable organ involvement in disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE206651 | GEO | 2023/01/31

REPOSITORIES: GEO

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Multi-organ single cell analysis of a mouse model of collagen-induced arthritis [subseries2]

Project description:Prioratization of disease associated mechanisms in immune-mediated inflammatory diseases (IMIDs) is complicated by altered interactions across multiple organs and cell types. We have adressed these challenges by analyzing a multi-organ multicellular disease model (MO-MCDM) of a mouse IMID model, namely collagen-induced arthritis (CIA). In this pilot study, we sequenced at least one healthy and one CIA sample from each of the ten organs, joint, lung, muscle, skin, spleen, blood, draining lymph nodes, thymus, liver, and kidney. Sequencing data from liver and kidney never reached our defined quality cut-off, and were thus excluded from further comparisions. Of the remaining organs, we found that joint, lung, muscle, skin, and spleen had the highest number of DEGs between CIA and healthy mice. We thus reason that these five organs shoult be most relevant to study disease associated changes on a systemic level, and prioritized those for further analyses.

2023-01-31 | GSE206654 | GEO

Bulk RNA-seq on paws of collagen-induced arthritis (CIA) mouse model at different disease stages

Project description:The goal of this experiment is to profile longitudinal transcriptome changes during the development of murine arthritis in CIA mouse model. Male DBA1 mice (age between 10 to 12 weeks) were used in this study. CIA was induced by two immunizations with Type II collagen in Complete Freund’s adjuvant (CFA) at day 0, and with Type II collagen in Incomplete Freund’s adjuvant (IFA) at day 21. Bulk RNA-seq were done on right hind paws from control (non-immunized DBA1 mice) and CIA mice at different disease stages (up to 10 weeks after 1st immunization).

2022-03-24 | GSE193335 | GEO

Gene expression profile in mouse back skin after cyclophosphamide treatment

Project description:Chemotherapy-induced hair loss (alopecia; CIA) is a highly distressing adverse effect that many cancer patients endure. Yet the molecular pathobiology of CIA remains largely unknown. We analysis the changes of mRNA profiles at different time points after cyclophosphamide treatment using Next-generation Sequencing in a mouse model of CIA. Our result revealed that Shh signaling is an evolutionarily conserved key target in CIA pathobiology.

2018-08-29 | GSE119118 | GEO

Collagen induced arthritis plasma proteomic analysis

Project description:The aim of the project is to analyze the plasma proteomic profile of an animal model of arthritis (Collagen Induced Arthritis; CIA) in response to different treatments. For this, plasma samples from mice under five different treatments were analyzed (N=6 per group): Vehicle, CIA, CIA + Δ9-THCA-A (20 mg / kg), CIA + Δ9-THCA-A (20 mg / kg) + T0070907 (5 mg / kg) and CIA + Δ9-THCA-A (20 mg / kg) + SR141716A (5 mg / kg).

2020-09-18 | PXD015274 | Pride

DNA methylation analysis of synovial fibroblasts from mice undergoing collagen-induced arthritis (CIA) treated, or not, with the the helminth-derived immunomodulator, ES-62

Project description:Aim: Synovial fibroblasts (SFs) undergo a rewiring of their DNA methylation landscape that is associated with their development of an aggressive pathogenic phenotype during Rheumatoid Arthritis (RA), both in humans and in CIA, a mouse model of this chronic inflammatory disease. The helminth-derived immunomodulator, ES-62 acts to prevent joint destruction in CIA by suppressing pathogenic SF responses. We therefore investigated whether ES-62 suppressed the changes in DNA methylation observed in SFs from CIA, relative to those from healthy, mice. Methods: The DNA methylation status of SFs from naïve (no induction of CIA), CIA and ES-62-treated mice undergoing CIA (CIA_ES-62) was compared by Reduced Representation Bilsulphite Sequencing (RRBS) analysis performed by the Active Motif service. Results: Synovial fibroblasts from naive, CIA and CIA_ES-62 mice exhibit differential genomic methylation profiles. Conclusion: ES-62 protection against joint protection in CIA is not associated with prevention of the changes in DNA methylation occurring during rewiring of naive SFs to aggressively pathogenic CIA SFs but rather, reflects generation of a distinct ES-62 phenotype of SF genomic methylation.

2021-03-01 | GSE158185 | GEO

Bulk RNA-seq on paws of collagen-induced arthritis (CIA) mouse model at different disease stages

Project description:Bulk RNA-seq on paws of collagen-induced arthritis (CIA) mouse model at different disease stages

| PRJNA795807 | ENA

Mouse CIA Cytokine Array

Project description:The molecular basis to autoimmune arthritis is unclear. Collagen Induced Arthritis (CIA) in mice, is a model that has many features that resemble Rheumatoid Arthritis (RA), although it does not perfectly duplicate RA. The study of CIA has provided insight into relevant pathogenesis and has aided in the identification of potential therapeutic targets. In this study we used Mouse Cytokine Expression Arrays to examine gene expression levels in joints at early, peak and decline stages during disease in DBA/1 mice. The aim of the study was to identify candidate molecules that may be involved in the development and progression of collagen-induced arthritis (CIA). Keywords: Disease State Analysis

2007-09-18 | GSE8915 | GEO

Comparative analysis of monocytes from healthy donors, patients with metastatic breast cancer, sepsis or tuberculosis.

Project description:Myeloid-derived suppressor cells (MDSCs) are highly immunosuppressive myeloid cells, which increase in cancer patients. The molecular mechanism behind their generation and function is unclear. Whereas granulocytic-MDSCs correlate with poor overall survival in breast cancer, the presence and relevance of monocytic-MDSCs (Mo-MDSCs) is unknown. Here we report for the first time an enrichment of functional blood Mo-MDSCs in breast cancer patients before they acquire a typical Mo-MDSC surface phenotype. A clear population of Mo-MDSCs with the typical cell surface phenotype (CD14+HLA-DRlow/-Co-receptorlow/-) increased significantly first during disease progression and correlated to metastasis to lymph nodes and visceral organs. Furthermore, monocytes, comprising the Mo-MDSC population, from patients with metastatic breast cancer resemble the reprogrammed immunosuppressive monocytes in patients with severe infections, both by their surface and functional phenotype but also at their molecular gene expression profile. Our data suggest that monitoring the Mo-MDSC levels in breast cancer patients may represent a novel and simple biomarker for assessing disease progression.

2015-02-03 | GSE65517 | GEO

Expression data from mouse arthritis tarsal joints

Project description:Pathological bone changes differ considerably between inflammatory arthritic diseases, and most studies have focused on bone erosion. Collagen Induced Arthritis (CIA) is a model for Rheumatoid Arthritis, which, in addition to bone erosion, demonstrates bone formation at the time for clinical manifestations. The objective of this study was to use the CIA model to study bone remodelling by performing a gene expression profiling time-course study on the CIA model.

2015-03-01 | GSE61140 | GEO

ERK signaling mediates resistance to immunomodulatory drugs in the bone marrow microenvironment (RNA-Seq)

Project description:Immunomodulatory drugs (IMiDs) have markedly improved patient outcome in multiple myeloma (MM); however, resistance to IMiDs commonly underlies relapse of disease. Here we identify and validate that TNF receptor associated factor protein family TRAF2 KD/KO in MM cells mediates IMiDs resistance via activation of non-canonical NF-kB and MEK-ERK signaling. Within MM bone marrow (BM) stromal cell supernatants, TNF-a induces proteasomal degradation of TRAF2, non-canonical NF-kB, and downstream ERK signaling in MM cells, whereas IL-6 directly triggers ERK activation. RNA sequencing of MM patient samples shows nearly universal ERK pathway activation at relapse on lenalidomide maintenance therapy, confirming its clinical relevance. Combination MEK inhibitor treatment restores IMiDs sensitivity of TRAF2 KO cells both in vitro and in vivo using an inducible TRAF2 KD MM xenograft model. Our studies provide the framework for clinical trials of MEK inhibitors to overcome IMiDs resistance in the BM microenvironment and improve patient outcome in MM.

2021-06-15 | GSE171340 | GEO

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