The embryonic origins of site-specific arthritis; Bulk RNA sequencing of CD34+(Pi16+) fibroblasts stimulated with TNF and IL1b.

In human fingers, proximal interphalangeal (PIP) joints are preferentially affected by inflammatory arthritis, whereas distal interphalangeal (DIP) joints are spared, providing a model to investigate the predilection of inflammation to distinct sites. We combine single-cell RNA sequencing, imaging and X-ray tomography to examine cellular composition, spatial organization and structure of finger joints during foetal development.

PIP joints were enriched for Pi16+ fibroblasts, which are located in perivascular regions and at tendon–ligament interfaces. To investigate whether Pi16+ fibroblasts have a specific response to inflammatory cytokines Pi16+ and Pi16- cells were sorted from foetal fingers using the co-expressed marker CD34. Thes cells were cultured in vitro with and without TNF and IL1b and analyzed using bulk RNA sequencing.