A stretch-responsive fibroblast program promotes epidermal stem cell self-renewal during skin expansion

Area of Science:

• Dermatology
• Tissue Engineering
• Developmental Biology

Background:

• Stretch-mediated tissue expansion is crucial for reconstructive surgery, requiring coordinated growth of epidermal and dermal layers.
• The precise mechanisms by which fibroblasts respond to mechanical stretching and support keratinocyte proliferation are not fully understood.

Purpose of the Study:

• To investigate the in vivo transcriptional response of fibroblasts to mechanical stretching.
• To elucidate how fibroblast behavior during tissue expansion influences epidermal stem cell self-renewal and overall skin regeneration.

Main Methods:

• In vivo transcriptional profiling of fibroblasts under mechanical stretching.
• Analysis of fibroblast proliferation, collagen production, and extracellular matrix remodeling.
• Assessment of epidermal stem cell self-renewal in a low-collagen environment mimicking fibroblast changes.

Main Results:

• Mechanical stretching induces fibroblasts to exit quiescence and enter a proliferative state.
• Fibroblasts downregulate collagen production and upregulate extracellular matrix remodeling factors, resembling an embryonic-like phenotype.
• A low-collagen state, driven by fibroblast reprogramming, enhances epidermal stem cell self-renewal.

Conclusions:

• Fibroblast reprogramming during tissue expansion is key to coordinating dermal and epidermal growth.
• Understanding these fibroblast dynamics offers insights for optimizing in vivo skin expansion techniques.
• This research provides a basis for improving the generation of in vitro skin grafts for clinical applications.