Gradients of Mesenchymal Stiffness Control Sweat Gland Cell Fate Specification During Morphogenesis

This study investigates how mesenchymal stiffness gradients influence sweat gland cell fate during morphogenesis. It was found that as sweat placode progenitors invaginate into the dermis, they first encounter a stiff environment that promotes ductal growth, followed by a softer environment that fosters glandular growth. This process is associated with differential Wnt expression by fibroblasts. Manipulating tissue stiffness and using a microfluidic device to create a Wnt gradient demonstrated that ductal-to-glandular fate transition occurs in response to these mechanical and biochemical cues. The findings highlight the interplay between mesenchymal niche and epidermal progenitors, offering insights for engineering skin regeneration with functional sweat glands.