A Cross‐Species Single‐Cell Transcriptomic Atlas of Subcutaneous Adipose Tissue Reveals Conserved and Divergent Cellular Programs

Adipose tissue is not only the primary site of energy storage but also an essential metabolic organ for maintaining energy homeostasis to regulate adipogenesis, metabolism, and chronic inflammation in mammals. However, the cross-species conservation and divergence of its cellular composition and transcriptional features remain unclear. To address this, we analyzed single-cell RNA sequencing datasets from cattle, pigs, and humans. Conserved cell types, including adipocytes, adipose stem and progenitor cells (ASPCs), macrophages, endothelial cells, and T cells, were identified across all three species. In contrast, pigs uniquely contained mesenchymal cells (COL1A1, COL1A2) and B cells (CD37), cattle possessed distinct preadipocyte populations (COL3A1, PNPLA2, GPAM), and humans exhibited abundant dendritic (HLA-DRA, HLA-DRB1) and mast cells (KIT). Focusing on adipocytes, we identified 537, 160, and 73 species-specific DEGs in cattle, pigs, and humans, respectively. Gene Ontology enrichment analysis of adipocyte-specific DEGs revealed that genes enriched in cattle were primarily involved in cytoskeletal organization and triglyceride biosynthesis (LPIN1, DGAT2), those enriched in pigs in oxidative phosphorylation and thermogenesis (LIPE, CIDEA), and those enriched in humans in lipid transport and immune signaling (ADIPOQ, LPL). Overall, this study establishes a cross-species single-cell atlas of subcutaneous adipose tissue, providing insights into conserved architectures and species-specific adaptations, and serving as a valuable resource for comparative biology and livestock research.