Cross-tissue single-cell transcriptomic landscape reveals the key cell subtypes and their potential roles in the nutrient absorption and metabolism in dairy cattle

[Display omitted] •Discover 55 cell types and their specific markers in the first single-cell atlas of cattle;•Identify and verify 3 epithelial progenitor-like cell subtypes in the forestomach•Reveal vital but nonimmune functions of neutrophils in the mammary gland;•Uncover key cell subtypes with preferential nutrient uptake;•Find Th17 cells regulate epithelial cells responding to nutrient transport in the forestomach. Dairy cattle are a vitally important ruminant in meeting the demands for high-quality animal protein production worldwide. The complicated biological process of converting human indigestible biomass into highly digestible and nutritious milk is orchestrated by various tissues. However, poorly understanding of the cellular composition and function of the key metabolic tissues hinders the improvement of health and performance of domestic ruminants. The cellular heterogeneity, metabolic features, interactions across ten tissue types of lactating dairy cattle were studied at single-cell resolution in the current study. Unbiased single-cell RNA-sequencing and analysis were performed on the rumen, reticulum, omasum, abomasum, ileum, rectum, liver, salivary gland, mammary gland, and peripheral blood of lactating dairy cattle. Immunofluorescences and fluorescence in situ hybridization were performed to verify cell identity. In this study, we constructed a single-cell landscape covering 88,013 high-quality (500