Single-cell analysis uncovers fibroblast heterogeneity and criteria for fibroblast and mural cell identification and discrimination

Male Cell- och molekylärbiologi Science Myocardium Q Myocytes, Smooth Muscle Urinary Bladder Cell Differentiation Mesenchymal Stem Cells Cell Separation Fibroblasts Flow Cytometry Coronary Vessels Article Muscle, Smooth, Vascular Extracellular Matrix Intestines Mice Animals RNA-Seq Single-Cell Analysis Muscle, Skeletal Pericytes Cell and Molecular Biology
DOI: 10.1038/s41467-020-17740-1 Publication Date: 2020-08-07T10:03:19Z
ABSTRACT
AbstractMany important cell types in adult vertebrates have a mesenchymal origin, including fibroblasts and vascular mural cells. Although their biological importance is undisputed, the level of mesenchymal cell heterogeneity within and between organs, while appreciated, has not been analyzed 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 and provide molecular signatures for cell subtype identification. We observe striking inter- and intra-organ heterogeneity amongst the fibroblasts, primarily reflecting differences in the expression of extracellular matrix components. Fibroblast subtypes localize to discrete anatomical positions offering novel predictions about physiological function(s) and regulatory signaling circuits. Our data shed new light on the diversity of poorly defined classes of cells and provide a foundation for improved understanding of their roles in physiological and pathological processes.
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