biostudies-literatureLi HNational Natural Science Foundation of ChinaNational Key Research and Development Program of China19https://www.ebi.ac.uk/biostudies/studies/S-EPMC9072607biostudies-literatureUnknown11(1)Animal models are widely used for biomedical studies and drug evaluation. The small intestine plays key roles in nutrient absorption, hormone secretion, microbiota defense and drug absorption and metabolism. Although the intestinal structure of mammals is conserved, the differences on epithelial cell composition, functional assignments and drug absorption among mammals are largely unknown. Here, cross-species analysis of single-cell transcriptomic atlas of the ileum epithelium from mouse, rat, pig, macaque and human reveals the conserved and differential cell types and functions among species, identifies a new CA7⁺ cell type in pig, macaque and human ileum, uncovers the distinct expression pattern in enterocytes, enteroendocrine cells and Paneth cells, and defines the conserved Cell regeneration (London, England)Cross-species single-cell transcriptomic analysis reveals divergence of cell composition and functions in mammalian ileum epithelium.PMC9072607317300562017YFA010360131988101Li HJi WZhang MHong FWang XWang HChen YGWang YZhao JCui AfalseCross-species single-cell transcriptomic analysis reveals divergence of cell composition and functions in mammalian ileum epithelium.Animal models are widely used for biomedical studies and drug evaluation. The small intestine plays key roles in nutrient absorption, hormone secretion, microbiota defense and drug absorption and metabolism. Although the intestinal structure of mammals is conserved, the differences on epithelial cell composition, functional assignments and drug absorption among mammals are largely unknown. Here, cross-species analysis of single-cell transcriptomic atlas of the ileum epithelium from mouse, rat, pig, macaque and human reveals the conserved and differential cell types and functions among species, identifies a new CA7⁺ cell type in pig, macaque and human ileum, uncovers the distinct expression pattern in enterocytes, enteroendocrine cells and Paneth cells, and defines the conserved 2022-01-01T00:00:00Z2022 May2025-04-04T03:19:57.291Z2025-04-04T03:19:57.291ZS-EPMC90726073551136110.1186/s13619-022-00118-7