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Fibrotic disorders are some of the most devastating and poorly treated conditions in developed nations, yet effective therapeutics are not identified for many of them. A major barrier for the identification of targets and successful clinical translation is a limited understanding of the human fibrotic microenvironment. Here, we construct a stromal cell atlas of human fibrosis at single cell resolution from patients with Dupuytren's disease, a localized fibrotic condition of the hand. A molecular taxonomy of the fibrotic milieu characterises functionally distinct stromal cell types and states, including a subset of immune regulatory ICAM1+ fibroblasts. In developing fibrosis, myofibroblasts exist along an activation continuum of phenotypically distinct populations. We also show that the tetraspanin CD82 regulates cell cycle progression and can be used as a cell surface marker of myofibroblasts. These findings have important implications for targeting core pathogenic drivers of human fibrosis.

Original publication

DOI

10.1038/s41467-020-16264-y

Type

Journal article

Journal

Nat commun

Publication Date

02/06/2020

Volume

11

Keywords

Actins, Biomarkers, Chemokines, CXC, Dupuytren Contracture, Fibrosis, Humans, Intercellular Adhesion Molecule-1, Molecular Medicine, Myofibroblasts, Stromal Cells, Tetraspanins, Tumor Microenvironment