Spatiotemporal decoding of skin biology: development, aging, disease, and regeneration

Abstract Skin shows distinct temporal dynamics and spatial heterogeneity during development, aging, disease, and regeneration. Although single-cell sequencing has revealed cellular diversity, its lack of spatial context limits the ability to characterize cells within their native tissue microenvironment. Factors such as acute injury and chronic wounds spatiotemporally disrupt skin homeostasis and induce complex remodeling and functional changes. Understanding these dynamic processes with spatiotemporal resolution remains a challenge in skin biology. Recent advances in spatiotemporal omics make it possible to integrate single-cell sequencing, spatial omics, and time series analyses, allowing the preservation of in situ cellular positions and revealing gene expression dynamics and intercellular networks. These technologies have reshaped the understanding of skin development and wound healing and have promoted advances in precision medicine and regenerative therapies. In this review, the applications of, recent advances in, and clinical translation potential of spatiotemporal omics in skin research are summarized. The construction of a high-resolution, spatiotemporal cellular atlas across the human skin life cycle will help identify key biomarkers, optimize regenerative strategies, and support personalized therapies.