Human Fibroblast-Myeloid Cell Tissue Atlas Across the Lungs, Synovium, Skin, and Heart

The availability of single-cell RNA sequencing (scRNAseq) data in different tissues and disease states provides an opportunity to compare cellular subsets and identify common and unique cellular activation. In this study, we aimed to characterize shared and tissue-specific myeloid and stromal phenotypes and to uncover key cellular subtypes involved in pathogenic tissue activation.

We analyzed scRNAseq data from 14 public data sets, comprising the heart (n = 41), lungs (n = 25), skin (n = 34), and synovium (n = 48) in healthy and diseased states. These data sets contained 136,741 myeloid cells and 116,776 fibroblasts. We tested Seurat, Harmony, and BBKNN for the integration of the data sets. We used immunofluorescence to validate identified common fibroblast and macrophage subsets in the various tissues.

Our analysis identified distinct and overlapping myeloid and stromal cell populations in the lungs, heart, skin, and synovium. Although myeloid populations were mostly similar between the analyzed organs, shared fibroblast populations were most evident in the skin and synovium and included POSTN⁺, APOE⁺, and MFAP5⁺ subsets. POSTN⁺ and MFAP5⁺ fibroblasts were localized in distinct tissue niches of the skin and synovium and showed heterogenous response in different diseases. SPP1⁺ macrophages and POSTN⁺ fibroblasts emerged as common pathogenic subsets in diseased tissues.

Despite significant interindividual variability, we identified both shared and disease-specific changes in myeloid and stromal cell populations. Our findings provide insights into the conserved and tissue-specific roles of myeloid and stromal cells in health and disease and contribute to a better understanding of tissue pathology and potential therapeutic targets.