Imaging mass cytometry-based characterisation of fibroblast subsets and their cellular niches in systemic sclerosis
Objectives Transcriptomic data demonstrated that fibroblasts are heterogeneous with functionally diverse subpopulations. Although fibroblasts are key effector cells of fibrotic diseases such as systemic sclerosis (SSc), they have not yet been characterised spatially at the cellular level. Here, we aimed to investigate fibroblast subpopulations using imaging mass cytometry (IMC) as a proteomic-based, spatially resolved omics approach. Methods We applied IMC to deconvolute the heterogeneity of 49 969 cells including 6501 fibroblasts at the single-cell level, to analyse their spatial distribution and to characterise their cellular niches in skin sections of patients with SSc and controls in situ. Results We identified 13 different subpopulations of fibroblasts in SSc and control skin, the proportion increases in five fibroblast subpopulations (myofibroblasts, FAPhigh, S1PR+, Thy1+;ADAM12high;PU.1high and ADAM12+;GLI1+ fibroblasts) and decreases in three subpopulations (TFAMhigh, PI16+;FAP
