Cellular census of human fibrosis defines functionally distinct stromal cell types and states

Thomas B. Layton, Lynn Williams, Fiona McCann, Mingjun Zhang, Marco Fritzsche, Huw Colin-York, Marisa Cabrita, Michael T. H. Ng, Marc Feldmann, Stephen N. Sansom, Dominic Furniss, Weilin Xie and Jagdeep Nanchahal ()
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Thomas B. Layton: University of Oxford
Lynn Williams: University of Oxford
Fiona McCann: University of Oxford
Mingjun Zhang: Celgene Corporation
Marco Fritzsche: University of Oxford
Huw Colin-York: University of Oxford, Headley Way
Marisa Cabrita: University of Oxford
Michael T. H. Ng: University of Oxford, Headley Way
Marc Feldmann: University of Oxford
Stephen N. Sansom: University of Oxford
Dominic Furniss: University of Oxford, Botnar Research Centre
Weilin Xie: Celgene Corporation
Jagdeep Nanchahal: University of Oxford

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract 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.

Date: 2020
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DOI: 10.1038/s41467-020-16264-y

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