Age- and Microbiota-Dependent Cell Stemness Plasticity Revealed by Cattle Cell Landscape

Area of Science:

• Animal Science
• Genomics
• Developmental Biology

Background:

• Newborn ruminants are functionally monogastric, and a lack of cellular understanding hinders health and performance improvements.
• Understanding cellular differences between newborn and adult ruminants is critical for optimizing livestock production.

Purpose of the Study:

• To create a comprehensive single-cell transcriptomic atlas of cattle across various tissues and life stages.
• To investigate the cellular mechanisms driving the postnatal development and functional maturation of ruminant digestive and associated organs.

Main Methods:

• Single-cell RNA sequencing was performed on 13 tissues from newborn and adult cattle.
• A total of 235,941 high-quality single cells representing 78 cell types were analyzed.
• A public database, Cattle Cell Landscape, was established for data accessibility.

Main Results:

• A detailed transcriptomic atlas revealed 78 distinct cell types, including a novel newborn-specific cell type, STOML3.
• Epithelial cells in the newborn forestomach (rumen, reticulum, omasum) showed greater transcriptional indistinctness compared to adults.
• Forestomach development is driven by progenitor cells with high DNA repair and methylation activity, influenced by the *Megasphaera* genus.

Conclusions:

• Age- and microbiota-dependent stemness plasticity in epithelial cells drives the functional maturity of ruminants.
• The study provides a valuable resource for understanding ruminant cell biology and improving animal health and performance.
• STOML3 cells play a key role in stemness maintenance within the hepatic microenvironment.