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

• DOI: 10.1038/s41467-020-17740-1
• Publication Date: 2020-08-07T10:03:19Z
• Authors: Lars Muhl; Guillem Genové; Stefanos Leptidis; Jianping Liu; Liqun He; Giuseppe Mocci; Ying Sun; Sonja Gustafsson; Byambajav Buyande...; Indira V. Chivukula; Åsa Segerstolpe; Elisabeth Raschpe...; Emil M. Hansson; Johan L. M. Björk...; Xiao-Rong Peng; Michael Vanlandew...; Urban Lendahl; Christer Betsholtz
• Keywords: 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

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.