High-Resolution Spatial Map of the Human Facial Sebaceous Gland Reveals Marker Genes and Decodes Sebocyte Differentiation.

The sebaceous gland (SG) is essential for skin homeostasis by producing sebum to lubricate and protect the skin. Dysfunctions in SG activity are associated with skin disorders such as acne, seborrheic dermatitis, and alopecia. However, its cellular and molecular mechanisms in humans remain poorly understood because most studies have been conducted in mouse models. This study provides a comprehensive molecular analysis of the human SG, focusing on cellular interactions; sebocyte differentiation; and to our knowledge, previously unreported gene markers. By integrating Stereo-seq spatial transcriptomics, single-cell RNA sequencing, and validation by multiplexed error-robust FISH, we identified 4 distinct stages of sebocyte differentiation, each characterized by unique gene signatures. These results reveal that sebocyte differentiation is a dynamic and complex process. Our findings enhance the understanding of SG biology and provide a valuable reference for future research and the development of therapies for SG-related disorders, including acne.