These activity indices showed increased SMAD3 regulon activity in a more restrictive pattern, the highest activity was in cluster 4 (SSc SFRP2hi fibroblasts) and enhanced in the region of the SFPR2hi, SFRP4+ myofibroblasts, as well as in cluster 8 (dermal sheath cells, Supplementary Fig. 24). This evidence concerns the gene SFRP4 and systemic sclerosis.