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

Authors

Guanghui Tan, Xiaoru Yan, Xuesha Cao, Ao Zhang, Tao Shi, Yaqi Zhou, Xi Guo, Haoping Wang, Hengkuan Li, Jiezhang Li, Yingran Liu, Xihong Wang, Yu Jiang, Yi Zheng

Published in

Genome biology. Jun 27, 2026. Epub Jun 27, 2026.

Abstract

Elucidating cellular hierarchies and regulatory mechanisms of placental development across gestation is critical for understanding pregnancy maintenance and improving reproductive outcomes in mammals, including cattle. However, a comprehensive, temporally resolved single-cell characterization of the bovine placenta has remained lacking.
We construct a longitudinal single-nucleus transcriptomic atlas comprising 311,299 placental cells and nuclei across 13 developmental timepoints (E12, E14, E16, E18, E24, E30, E50, E60, E85, E110, E180, E240, and E280). We identify 13 major cell types and 14 trophoblast subtypes, revealing pronounced cellular heterogeneity and stage-specific transcriptional programs. Regulatory analyses highlight HAND1 and DLX5 as candidate key regulators of maternal recognition of pregnancy. Trajectory inference demonstrates that binucleate cells arise from specific uninucleate cell subpopulations around E24, with differentiation governed by genomic imprinting and metabolic reprogramming. Integration with genome-wide association study data identifies eight early trophoblast subtypes significantly associated with gestation length, along with candidate pathways and risk genes, including CYCS, HMGA1, and VDAC1, under strong evolutionary constraint. Additionally, we find that placental macrophages emerge from E30 in cattle and show significant associations with pregnancy loss in both cattle and humans, sharing conserved risk pathways.
This study provides a comprehensive spatiotemporal single-cell atlas of bovine placental development, defining cellular hierarchies, lineage dynamics, and regulatory networks at the maternal-fetal interface. These findings offer a valuable resource and conceptual framework for understanding pregnancy maintenance and for improving reproductive traits in ruminants.

PMID:
42365320
Bibliographic data and abstract were imported from PubMed on 28 Jun 2026.

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