Fibroblast-like synoviocytes (FLS) are cells that line the joint surfaces.  Synovial FLS are further subdivided into lining and sub-lining cells.  Recent human patient based single cell studies have demonstrated that FLS play a critical role in the pathology of inflammatory joint diseases (IJD) including rheumatoid arthritis (RA). It is now well established that in response to chronic inflammation, FLS are activated and adopt a pro-inflammatory aggressive state where they start to express pro-inflammatory genes, increase in numbers and move over into the joint spaces contributing to synovitis, articular cartilage and bone degradation. This pathological activation of FLS is further considered to adopt an irreversible epigenetic memory that is harmful to the synovium and the articular joint.  Recent advancement in single cell technologies have made it possible to identify new single cell subtypes of mesenchymal, endothelial and immune cell clusters in the pathological tissue including the IJD synovium.  Single cell technologies have been useful in understanding the disease etiology from patient derived biopsy samples but these studies lack in understanding the longitudinal study of disease progression. Hence it is now eminent for the development of new disease inducible mice models that can help study the tissue architecture before, after and during the disease stages of IJD.  The overall goal of this project is to develop an inducible mice model for inflammatory joint disease (IJD) and apply single cell technologies to isolate activated FLS cells from the inflamed synovium before, after and during the disease stages.  Further we will apply state of the art Fluorescence-activated cell sorting (FACS) and sequencing technologies to understand disease transcriptomic and cell profiles of IJD synovium, before after and during the disease progression.  To achieve this we adapted Wixler et.al., inducible human TNF transgene (ihTNFtg) to express tdtomato exclusives in the synovium.