Epidermal-Dermal Coupled Spheroids Are Important for Tissue Pattern Regeneration in Reconstituted Skin Explant Cultures

The study investigates the formation and function of epidermal-dermal coupled spheroids, known as competent morphogenetic units (CMUs), in skin explant cultures and their role in tissue patterning and hair regeneration. Using single-cell RNA sequencing (scRNA-seq), the researchers analyzed the emergence of new cell types and molecular interactions during CMU formation. They discovered that IFNγ signaling induces apical-basal polarity in epidermal cells, TGFβ from the dermis prompts basement membrane formation, and VEGF signaling is crucial for dermal cell attachment to the epidermal cyst shell. The study also found that adult mouse and human fetal scalp cells generally do not form CMUs, but this ability can be restored with IFNγ or VEGF, leading to hair regeneration. The findings suggest that manipulating multicellular configurations and molecular pathways can enhance morphogenetic competence and regeneration in skin, which has implications for in vitro morphogenesis and developing new regeneration strategies. Specific numbers of subjects or experimental replicates were not provided in the summary.