ABSTRACT
Skin and lung fibrosis in systemic sclerosis (SSc) is driven by myofibroblasts, alpha-smooth muscle actin expressing cells that arise from a variety of cell types in murine fibrosis models. Utilizing single cell RNA-sequencing to examine the transcriptome changes, we show that SSc dermal myofibroblasts arise from an SFRP2/DPP4-expressing progenitor fibroblast population that globally upregulates expression of transcriptome markers, such as PRSS23 and THBS1. Only a fraction of SSc fibroblasts differentiate into myofibroblasts, as shown by expression of additional markers, SFRP4 and FNDC1. The myofibroblast transcriptome implicates upstream transcription factors that drive myofibroblast differentiation.
Competing Interest Statement
Dr. Lafyatis reports grants from Bristol Meyer Squib, Corbus, Formation, Moderna, Regeneron, Pfizer, and Kiniksa, outside the submitted work; and served as a consultant with Bristol Meyers Squibb, Formation, Sanofi, Boehringer-Ingelheim, Merck, and Genentech/Roche.
Footnotes
Disclosures Dr. Lafyatis reports grants from Bristol Meyer Squib, Corbus, Formation, Moderna, Regeneron, Pfizer, and Kiniksa, outside the submitted work; and served as a consultant with Bristol Meyers Squibb, Formation, Sanofi, Boehringer-Ingelheim, Merck, and Genentech/Roche.