Multispecies Transcriptomics of Mammalian Skin Reveals Conserved and Divergent Regulatory Features

Skin is a highly specialized barrier organ, which serves essential barrier, immune, and sensory functions and exhibits conserved structure. In addition, each species exhibits a unique skin transcriptional profile for adapting distinct environmental conditions and physiological demands. However, these transcriptional profiles across mammals remain incompletely understood. In this study, we integrated 61 publicly available skin RNA-seq datasets from eight mammalian species: human (Homo sapiens), macaque (Macaca fascicularis), mouse (Mus musculus), sheep (Ovis aries), goat (Capra hircus), donkey (Equus asinus), rabbit (Oryctolagus cuniculus), and pig (Sus scrofa). We identified a large number (2286 to 4588) of differentially expressed genes (DEGs) based on 10,504 one-to-one orthologous genes in all pairwise species comparisons. A total of 44 conserved genes were identified by integrating tissue specificity, expression variability, and mean expression level, which were enriched in epidermal development, keratinocyte differentiation, and desmosome organization. We also identified species-specific genes and transcription factors, such as STMN1 (donkey), COL1A1 (goat), and ACTN2 (mouse), which are associated with the cell cycle, extracellular matrix, and muscle contraction pathways, respectively. WGCNA further revealed goat-associated module 2 (M2) enriched in the negative regulation of angiogenesis. Collectively, this study provides a comprehensive cross-species transcriptional profile resource for mammalian skin, providing a valuable resource for understanding the regulatory plasticity underlying skin evolution across mammals.