TY - JOUR
T1 - Single-cell analysis uncovers fibroblast heterogeneity and criteria for fibroblast and mural cell identification and discrimination
AU - Muhl, Lars
AU - Genové, Guillem
AU - Leptidis, Stefanos
AU - Liu, Jianping
AU - He, Liqun
AU - Mocci, Giuseppe
AU - Sun, Ying
AU - Gustafsson, Sonja
AU - Buyandelger, Byambajav
AU - Chivukula, Indira V.
AU - Segerstolpe, Åsa
AU - Raschperger, Elisabeth
AU - Hansson, Emil M.
AU - Björkegren, Johan L.M.
AU - Peng, Xiao Rong
AU - Vanlandewijck, Michael
AU - Lendahl, Urban
AU - Betsholtz, Christer
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Many 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.
AB - Many 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.
UR - http://www.scopus.com/inward/record.url?scp=85089186227&partnerID=8YFLogxK
U2 - 10.1038/s41467-020-17740-1
DO - 10.1038/s41467-020-17740-1
M3 - Article
C2 - 32769974
AN - SCOPUS:85089186227
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3953
ER -