Cluster Analysis Characterising the 3D Spatial Configuration of Human Epidermal Merkel Cells

Merkel cells (MCs) are connected to sensory fibres in the skin and contribute to tactile perceptions by acting as mechanoreceptors. MCs in the skin have been reported to be distributed in clusters or to be scattered. While the structural characteristics of MCs may influence tactile perceptions, conventional studies using skin sections could only assess those structures in limited regions. Here, we conducted extensive three-dimensional observations of MCs in epidermal sheets and examined their clustering patterns based on intercellular distances. Skin specimens from female donors at different ages (27, 34, 62, 84 and 91 years old) varied in MC density ranging from 6.7 to 26.4 mm^-2. Theoretically, a higher density of MCs would lead to the formation of short-distance clusters, but our results demonstrate that skin with the lowest MC density had a clustering pattern similar to skin with the highest MC density. These results indicate that inter-donor variation in MCs cannot be explained solely by uniform changes in MC density but rather reflects heterogeneous distribution patterns with distinct clustering configurations. Our pilot study provides insight into skin physiology and pathology by considering the spatial configuration of various types of skin cells, such as MCs, Langerhans cells and melanocytes.