Interfollicular Stem Cells of Human Epidermis Exhibit a Distinct Mechanical Signature That Deteriorates With Aging

Skin homeostasis and self-renewal are partially maintained by interfollicular stem cells (ISCs), located in the basal layer above the dermal papillae of the dermo-epidermal junction (DEJ). Aging leads to a decline in skin renewal and a concurrent reduction in stem cell potential. It is also marked by disorganization of the extracellular matrix in both the DEJ and dermis, and flattening of the DEJ. To better understand ISCs aging, new methods are needed to characterize ISCs and their environment. Since mechanical properties of cells and their substrate influence cell fate, we employed atomic force microscopy to explore whether ISCs niches and the DEJ exhibit distinct mechanical properties. Our findings reveal that ISCs possess greater stiffness than other basal cells, a mechanical signature that diminishes with age. Additionally, the DEJ beneath ISCs shows higher stiffness than under other basal cells, providing ISCs with a specific mechanical environment, which also deteriorates during aging. Finally, sorting of ISCs based on MCSP expression allowed us to enrich a putative ISC-like subpopulation located above the dermal papillae. The study of ISCs mechanical signatures offers a promising approach for characterizing 3D skin models and understanding defects in skin renewal and wound healing.