Melanocytes in congenital nevi secrete type I, III, VI collagens and possess matrix remodeling potential

Melanocytic nevi are characterized by nevus nests encapsulated by dense collagen networks. While fibroblasts are classically considered the primary source of extracellular matrix, they are remarkably sparse within these nests. Here, utilizing single-cell RNA sequencing on primary congenital nevus cells, we identify a specialized melanocyte subpopulation, termed ECM_Melanocytes. Trajectory and interactome analyses reveal their fibroblast-like signaling patterns. We demonstrate at both the tissue and cellular levels that these melanocytes autonomously synthesize and secrete type I, III, and VI collagens. Furthermore, they express and release matrix metalloproteinases MMP1 and MMP3, which co-localize with the surrounding collagen framework. Overall, we provide the first evidence that melanocytes secrete type I, III, and VI collagens and MMP1/3. This distinct behavioral pattern reveals that nevus cells are not merely residents in the tissue microenvironment, but its active constructors.