Exploring the Role of Fibroblast Heterogeneity from Different Skin Types in Epidermal Regeneration In Vitro

In human skin, dermal fibroblasts play a crucial role in epidermal regeneration and homeostasis. Despite literature highlighting fibroblast heterogeneity, physiological diversity in skin of color may impact in vitro approaches to investigating skin regeneration. We have investigated the functionality of human adult fibroblasts from different skin types in the morphogenesis of the epidermis in vitro. Primary papillary dermal fibroblasts and keratinocytes from donors with both darker (of African descent) and lighter (of European descent) skin types were used to reconstruct skin in vitro. Autologous skin models from the same donor were generated and compared with mixed skin models combining keratinocytes from one skin type with fibroblasts from the other. Papillary fibroblasts from African descent expressed a reduced amount of types IV and VII collagens at the dermal-epidermal junction in vitro. Morphogenesis of the reconstructed epidermis was differently regulated by the underlying papillary fibroblasts. European-descent fibroblasts increased the commitment of keratinocytes to a differentiated state in vitro, whereas African-descent fibroblasts maintained the proliferation of basal keratinocytes. Altogether, this study highlights how the skin type origin of fibroblasts can drive the phenotype of in vitro skin models. This sheds light on the heterogeneity of the superficial dermal layer and its specific dermal-epidermal crosstalk, providing insights into the cutaneous physiology of different skin types.