Abstract: Objective　To explore the cellular turnover and biological mechanisms underlying the spontaneous regression of giant congenital melanocytic nevus（ GCMN）. Methods　10× single-cell RNA sequencing was performed on normal skin， depigmented nevus， and non-regressed nevus from patients with spontaneous regressed GCMN. Raw data were first used to quantify gene expression， followed by dimensionality reduction， clustering， cell population identification， and visualization. Cell populations were annotated based on differentially expressed genes （DEGs）， and pathway enrichment and visualization of DEGs were carried out. Finally， histological staining was performed for validation. Results　 In GCMN， melanocytes constituted the largest proportion. During the regression process， the number of melanocytes decreased， while keratinocytes and fibroblasts increased. Immune cells exhibited a coexistence of both immune activation and suppression. In regressed tissues， melanocytes also expressed keratinocyte marker genes， while fibroblasts were enriched in pathways related to proliferation and extracellular matrix. Immunofluorescence staining revealed cells co-expressing SOX10 and Keratin， and pseudotime analysis indicated a transition of melanocytes into keratinocytes. Conclusion　The regression of GCMN is a longterm chronic inflammatory process， during which melanocytes undergo transformation and detach from the epidermal layer. Fibroblasts contribute to tissue repair and reconstruction.

Key words: Giant congenital pigmented nevus, 　Single-cell sequencing, 　Tumor microenvironment