Three-dimensional spatial transcriptomics uncovers cell type localizations in the human rheumatoid arthritis synovium

The inflamed rheumatic joint is a highly heterogeneous and complex tissue with dynamic recruitment and expansion of multiple cell types that interact in multifaceted ways within a localized area. Rheumatoid arthritis synovium has primarily been studied either by immunostaining or by molecular profiling after tissue homogenization. Here, we use Spatial Transcriptomics, where tissue-resident RNA is spatially labeled in situ with barcodes in a transcriptome-wide fashion, to study local tissue interactions at the site of chronic synovial inflammation. We report comprehensive spatial RNA-Seq data coupled to cell type-specific localization patterns at and around organized structures of infiltrating leukocyte cells in the synovium. Combining morphological features and high-throughput spatially resolved transcriptomics may be able to provide higher statistical power and more insights into monitoring disease severity and treatment-specific responses in seropositive and seronegative rheumatoid arthritis.

发炎的风湿性关节是一种高度异质性且结构复杂的组织，其内部多种细胞类型会被动态招募并扩增，且在局部区域内以多维度方式相互作用。既往针对类风湿关节炎滑膜的研究，主要采用免疫染色或组织匀浆后的分子谱分析手段开展。本研究采用空间转录组学（Spatial Transcriptomics）技术，以转录组全域范围内的条形码对组织原位驻留RNA进行空间标记，以此探究慢性滑膜炎症部位的局部组织相互作用。本研究报道了一组全面的空间RNA测序数据，结合了滑膜内浸润性白细胞有序结构及其周边区域的细胞类型特异性定位模式。将形态学特征与高通量空间分辨转录组学相结合，有望为血清阳性及血清阴性类风湿关节炎的病情严重程度监测与治疗特异性应答评估提供更高的统计效力与更深入的研究视角。