The placenta, a complex and organized supporting organ connecting the mother and fetus, guarantees the exchange of substances and hormone production for the successful maintenance of pregnancy 1. We provide a comprehensive single-cell data resource to shed light on future mechanistic studies of the gene regulatory networks governing hemochorial placentation. We map lineage differentiation trajectories and find that sinusoid trophoblast giant cells arise from the subpopulation of ectoplacental cone cells. Based on transcriptomic regulatory network inference, we specify transcription factors responsible for the regulation of dynamic developmental processes during lineage diversification. An updated differentiation roadmap of mouse trophoblast lineages is presented following systematic transcriptome analyses. We identify distinct trophoblast cell types during mouse placentation, including unreported progenitor cells and intermediate precursor cells. To decipher cell compositions and developmental processes, we systematically profile the single-cell transcriptomes of trophoblast cells from extraembryonic tissues (embryonic day 7.5 (E7.5) and E8.5) and placentae (E9.5–E14.5) at one-day intervals.

Due to the limitations of conventional research approaches, we are still far from a comprehensive understanding of mouse placentation, especially regarding the differentiation of trophoblast lineages at the early developmental stage.

The placenta is one of the most important yet least understood organs.

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