Pan-disease fibroblast atlas in skin fibrosis, inflammation, and cancer

The term fibroblast encompasses different stromal cell subpopulations. Single-cell technologies now enable granular definition of cell states, and shared fibroblast states across different human tissues in health and disease have been reported. However, a comprehensive analysis of fibroblast states across different disease contexts in a single organ has not been performed.

Here we utilise single-cell RNA sequencing from >300 000 human fibroblast cells in skin from health and 23 diseases to define fibroblast subpopulations. We identified 6 fibroblast subclusters in health and resolved their location in human skin tissue at single-cell resolution. In disease, we identified the presence of 3 novel states (F6: Myofibroblast, F6: Myofibroblast chemokine-high, and F7: Myofibroblast fascia-like) and polarisation of two cell states observed in healthy skin from disease (F1: Superficial regenerative and F3 CCL19+ Immune-interacting ADAMDEC1+/CXCL9+).