A longitudinal single-nucleus transcriptomic atlas of bovine placentation reveals dynamic cellular hierarchies and regulatory programs

Here, we constructed a single-nucleus transcriptomic atlas of 304,726 placental nuclei spanning 13 developmental stages in cows, identifying 13 major cell types and 14 trophoblast subtypes. Bioinformatics analyses and multiple validation experiments suggested that placental trophoblast cells exhibited stage-specific differences across gestation, and identified HAND1 and DLX5 as novel key regulators of maternal recognition of pregnancy.

We found that binucleate (BNC) cells arise from specific uninucleate (UNC) subpopulations at E24, with their differentiation trajectories co-regulated by imprinted genes and metabolic reprogramming. Integrated genome-wide association study (GWAS) analysis identified early trophoblast subtypes significantly associated with gestation length, along with key pathways and risk genes (e.g., CYCS, HMGA1, VDAC1), with these signals under strong evolutionary constraint.