Abstract
ABSTRACT Cellular and molecular characterization of mammals with multi‐chambered stomachs is crucial to our understanding of evolution in digestive and metabolic systems. Here, we generate single‐cell transcriptomic atlases of 253,448 and 279,057 cells from 54 tissues in camels and cattle, discovering 124 cell types. Cross‐species comparisons at four developmental stages reveal a common evolutionary origin among camel glandular sac, third‐chambered stomach, and bovine abomasum, with the camel lineages uniquely harboring a cell population characterized by heightened expression of genes involved in cell proliferation. Also, the advantages of camel hepatocytes in prevention of excessive fat deposition are uncovered. Interestingly, the spatial transcriptomic analysis further reveals a unique population of S100A4 + vascular smooth muscle cells in camel rather than other mammalian kidneys, potentially involved in prevention of renal hypertension. Altogether, our study provides invaluable resources for evolutionary biology and highlights cellular innovations underlying mammalian adaptation.