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Human Nail Single-Cell Landscape Identifies KRT19+ NSCs and SOX2/SOX9-WNT Regulated Differentiation

ABSTRACT: Nail stem cells (NSCs) are crucial for nail growth and fingertip regeneration, yet their identity and regulatory mechanisms remain unclear. Here, we used single-cell RNA sequencing to construct a spatiotemporal landscape of nine clusters of human nail epithelial cells. Through analysis of their bidirectional differentiation, we identified a KRT19+ subpopulation capable of differentiating into both nail structure and peri-nail epithelium. Our findings reveal that SOX2-controlled WNT signaling is inhibited in the proximal nail matrix, activated in the distal nail matrix, and subsequently downregulated by SOX9 towards the nail bed, guiding the orderly OFF-ON-OFF regulation of KRT19+ NSC differentiation into nail structure epithelium. In vivo validation using mouse models and human samples confirmed the regenerative capacity of KRT19+ NSCs. This study is the first to identify KRT19+ NSCs using a human nail single-cell atlas and elucidate their key regulatory mechanisms, providing a foundation for nail and digit regeneration therapies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE295702 | GEO | 2026/04/25

REPOSITORIES: GEO

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