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
AUTHORS (18)
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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