PI16 and rheumatoid arthritis: Interestingly, in the highest resolution of our matrix-focused clustering, we observed the presence of the PI16 + “universal” fibroblast subset defined in both mouse and human datasets by several groups (Buechler et al, 2021; Korsunsky et al, 2022), particularly highlighted by matrix glycoprotein IGFBP5. The primary function of IGFBP5 is the inhibition of IGF1 signalling, critically dysregulated in inflammatory hyperplasic conditions such as RA, both as described in the literature and this study (Andersson et al, 2018), through direct binding to IGF1 (Kalus et al, 1998).