Mechanical force drives the initial mesenchymal-epithelial interaction during skin organoid development

Area of Science:

• Stem cell biology
• Developmental biology
• Regenerative medicine

Background:

• Stem cells self-organize into organoids mimicking mini-organs.
• The mechanism initiating organoid-forming potential is unclear.
• Skin organoids offer a model to study hair follicle regeneration.

Purpose of the Study:

• Investigate how mechanical force drives initial epidermal-dermal interaction in skin organoids.
• Elucidate the role of mechanical-chemical coupling in potentiating hair follicle regeneration.
• Understand the fundamental mechanisms of organoid development and regeneration.

Main Methods:

• Live imaging and single-cell RNA-sequencing to analyze dermal cell contractile force.
• Calcium probe detection and functional perturbations to study calcium signaling pathways.
• In vitro mechanical loading and transplantation assays to assess Piezo1 expression and regenerative capacity.

Main Results:

• Dermal cell contraction initiates mesenchymal-epithelial interaction (MEI).
• Calcium signaling pathway regulates dermal cytoskeleton and dermal-epidermal attachment.
• Epidermal Piezo1 activation by mechanical force drives MEI and regulates dermal cell attachment.
• Proper initial MEI is essential for hair regeneration in transplanted skin organoids.

Conclusions:

• A mechanical-chemical cascade drives initial MEI in skin organoid development.
• This process is fundamental for organoid development and regenerative biology.
• Understanding these forces is key to advancing organoid-based regenerative therapies.