The inflamed rheumatic joint represents a highly heterogeneous and complex tissue due to the recruitment and expansion of multiple cell types that interact in a multifaceted ways within a localized area. Rheumatoid arthritis synovium has primarily been studied either by immunocytochemistry or after tissue homogenization; here, we provide spatially resolved transcriptomic analyses to demonstrate a systematic approach to studying local cellular ecosystem interactions at a site of chronic inflammation. We apply the spatial transcriptomics technology, where tissue-resident RNA is spatially labeled in situ with barcodes in a transcriptome-wide fashion. We report comprehensive spatial RNA-seq data coupled to quantitative and morphological single cell features from two disease-affected joints. Spatial tissue maps uncovered cell type-specific chemokine-driven dynamics at and around organized structures of infiltrating leukocyte cells in the synovium. These tertiary lymphoid organ infiltrations showed chemokine-driven dynamics in their centers and MZB1+XBP1+ edges. Distinct signatures extended in a radial fashion around the structures, with neighboring areas exhibiting fibroblast activation and macrophage stimulation in an activity gradient throughout the tissue volume.

 

Please visit our public github repo at: https://github.com/klarman-cell-observatory/3dst/

 

For questions, please contact Sanja Vickovic (vickovic@broadinstitute.org). 

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