A Stretch-Responsive Fibroblast Program Promotes Epidermal Stem Cell Self-Renewal During Skin Expansion

The study examines how dermal fibroblasts respond to mechanical stretching and influence epidermal stem cell behavior during skin expansion, using a mouse model with 32 subjects. It was found that stretching induces a fibroblast program characterized by reduced collagen deposition and increased proliferation, promoting epidermal stem cell self-renewal. Single-cell RNA sequencing revealed transcriptional changes in fibroblasts, particularly in the upper dermis, with upregulation of genes associated with extracellular matrix remodeling and an embryonic-like regenerative state. The research highlights the dynamic interaction between fibroblasts and keratinocytes, suggesting that fibroblasts play a crucial role in skin expansion by rapidly altering their transcriptional landscape, which has implications for understanding skin regeneration and repair mechanisms.