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

Introduction: 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.

Objectives: The cellular heterogeneity, metabolic features, interactions across ten tissue types of lactating dairy cattle were studied at single-cell resolution in the current study.

Methods: 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.

Results: In this study, we constructed a single-cell landscape covering 88,013 high-quality (500 < genes < 4,000, UMI < 50, 000, and mitochondrial gene ratio < 40% or 15%) single cells and identified 55 major cell types in lactating dairy cattle. Our systematic survey of the gene expression profiles and metabolic features of epithelial cells related to nutrient transport revealed cell subtypes that have preferential absorption of different nutrients. Importantly, we found that T helper type 17 (Th17) cells (highly expressing and ) were specifically enriched in the forestomach tissues and predominantly interacted with the epithelial cell subtypes with high potential uptake capacities of short-chain fatty acids through IL-17 signaling. Furthermore, the comparison between cells (epithelial cells with and expression levels both greater than 0.25) and other cells explained the importance of Th17 cells in regulating the epithelial cellular transcriptional response to nutrient transport in the forestomach.

Conclusion: The findings enhance our understanding of the cellular biology of ruminants and open new avenues for improved animal production of dairy cattle.