Myofibroblast transcriptome indicates SFRP2hi fibroblast progenitors in systemic sclerosis skin

Tracy Tabib, Mengqi Huang, Nina Morse, Anna Papazoglou, Rithika Behera, Minxue Jia, Melissa Bulik, Daisy E. Monier, Panayiotis V. Benos, Wei Chen, Robyn Domsic and Robert Lafyatis ()
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Tracy Tabib: Department of Medicine
Mengqi Huang: Department of Medicine
Nina Morse: Department of Medicine
Anna Papazoglou: Department of Medicine
Rithika Behera: Department of Medicine
Minxue Jia: Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh
Melissa Bulik: Department of Medicine
Daisy E. Monier: Department of Medicine
Panayiotis V. Benos: Department of Computational and Systems Biology, School of Medicine, University of Pittsburgh
Wei Chen: Department of Pediatrics, School of Medicine, University of Pittsburgh
Robyn Domsic: Department of Medicine
Robert Lafyatis: Department of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract Skin and lung fibrosis in systemic sclerosis (SSc) is driven by myofibroblasts, alpha-smooth muscle actin expressing cells. The number of myofibroblasts in SSc skin correlates with the modified Rodnan skin score, the most widely used clinical measure of skin disease severity. Murine fibrosis models indicate that myofibroblasts can arise from a variety of different cell types, but their origin in SSc skin has remained uncertain. Utilizing single cell RNA-sequencing, we define different dermal fibroblast populations and transcriptome changes, comparing SSc to healthy dermal fibroblasts. Here, we show that SSc dermal myofibroblasts arise in two steps from an SFRP2hi/DPP4-expressing progenitor fibroblast population. In the first step, SSc fibroblasts show globally upregulated expression of transcriptome markers, such as PRSS23 and THBS1. A subset of these cells shows markers indicating that they are proliferating. Only a fraction of SFRP2hi SSc fibroblasts differentiate into myofibroblasts, as shown by expression of additional markers, SFRP4 and FNDC1. Bioinformatics analysis of the SSc fibroblast transcriptomes implicated upstream transcription factors, including FOSL2, RUNX1, STAT1, FOXP1, IRF7 and CREB3L1, as well as SMAD3, driving SSc myofibroblast differentiation.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24607-6

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DOI: 10.1038/s41467-021-24607-6

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