Single-cell analysis uncovers inter- and intra-organ fibroblast heterogeneity and provides criteria for fibroblast identification and discrimination from vascular mural cells (Colon)

Many important cell types in adult vertebrates have a mesenchymal origin, including fibroblasts and vascular mural cells (pericytes and smooth muscle cells). Although their biological importance is undisputed, the level of mesenchymal cell heterogeneity within and between organs, while appreciated, has not been analysed in detail. Here, we compare single-cell transcriptional profiles of fibroblasts and vascular mural cells across four murine muscular organs: heart, skeletal muscle, intestine and bladder. We reveal gene expression signatures that demarcate fibroblasts from mural cells across these four as well as other organs and provide molecular signatures for cell subtype identification. Striking inter- and intra-organ heterogeneity and specialization were observed amongst the fibroblasts, primarily reflecting differences in the expression of extracellular matrix components. In comparison, mural cells appeared more homogenous. Fibroblast subtypes localize to discrete anatomical positions in all four organs, offering novel predictions about physiological function(s) and regulatory signalling circuits. Our data shed new light on the diversity and relationships between hitherto poorly defined classes of cells and provide a foundation for improved understanding of their roles in physiological and pathological processes. single-cell transcriptomes were generated of individual cells captured from adult male mice (10-20 weeks of age) by single-cell RNA-sequencing